Pregnancies in women with Turner syndrome: a retrospective multicentre UK study.

OBJECTIVE: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. DESIGN: Retrospective 20-year cohort study (2000-20). SETTING: Sixteen tertiary referral maternity units in the UK. POPULATION OR SAMPLE: A total of 81 women with Turner syndrome who became pregnant. METHODS: Retrospective chart analysis. MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes. RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. CONCLUSIONS: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. TWEETABLE ABSTRACT: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection.

Comparison of visual and computerised antenatal cardiotocography in the prevention of perinatal morbidity and mortality. A systematic review and meta-analysis.

INTRODUCTION: Antenatal cardiotocography (CTG) is used to monitor fetal well-being. There are two methods: visual (vCTG) or computerised (cCTG). An earlier Cochrane review compared the effects of both approaches on maternal and fetal outcomes. The objective of this systematic review was to update this search and identify studies not included in the Cochrane review. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL and MIDIRS databases were searched up to February 2021. We included randomised controlled trials (RCT) and non-randomised studies (NRS) of pregnant women receiving antenatal CTG with comparison of cCTG to vCTG and clinical outcomes. The Cochrane Risk of Bias Tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment. Data is presented as risk ratios with 95% confidence intervals and I2 is used as the statistical measure of heterogeneity. RESULTS: Three RCTs and three NRS were included. Meta-analysis of RCTs demonstrated a non-significant reduction in all-cause perinatal mortality (RR 0.23 [95%CI 0.04-1.30]), preventable perinatal mortality excluding congenital anomalies (RR 0.27 [95% CI 0.05-1.56]) and cesarean section (RR 0.91 [95%CI 0.68-1.22]). All RCTs included high-risk women and had a high risk of bias. There was one antenatal stillbirth across the three RCTs (n = 497). The NRS were at high-risk of bias and statistical analysis was not possible due to heterogeneity. Individual findings suggest reduced investigation and better prediction of neonatal outcomes with cCTG. CONCLUSIONS: There is a non-significant reduction in perinatal mortality with cCTG. Despite no clear reduction in perinatal mortality and morbidity with cCTG, it is objective and may reduce time spent in hospital and further investigations for women.

COngenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: prospective cohort study and systematic review.

OBJECTIVE: To determine the incremental yield of antenatal exome sequencing (ES) over chromosomal microarray analysis (CMA) or conventional karyotyping in prenatally diagnosed congenital heart disease (CHD). METHODS: A prospective cohort study of 197 trios undergoing ES following CMA or karyotyping owing to CHD identified prenatally and a systematic review of the literature were performed. MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov (January 2000 to October 2019) databases were searched electronically for studies reporting on the diagnostic yield of ES in prenatally diagnosed CHD. Selected studies included those with more than three cases, with initiation of testing based upon prenatal phenotype only and that included cases in which CMA or karyotyping was negative. The incremental diagnostic yield of ES was assessed in: (1) all cases of CHD; (2) isolated CHD; (3) CHD associated with extracardiac anomaly (ECA); and (4) CHD according to phenotypic subgroup. RESULTS: In our cohort, ES had an additional diagnostic yield in all CHD, isolated CHD and CHD associated with ECA of 12.7% (25/197), 11.5% (14/122) and 14.7% (11/75), respectively (P = 0.81). The corresponding pooled incremental yields from 18 studies (encompassing 636 CHD cases) included in the systematic review were 21% (95% CI, 15-27%), 11% (95% CI, 7-15%) and 37% (95% CI, 18-56%), respectively. The results did not differ significantly when subanalysis was limited to studies including more than 20 cases, except for CHD associated with ECA, in which the incremental yield was greater (49% (95% CI, 17-80%)). In cases of CHD associated with ECA in the primary analysis, the most common extracardiac anomalies associated with a pathogenic variant were those affecting the genitourinary system (23/52 (44.2%)). The greatest incremental yield was in cardiac shunt lesions (41% (95% CI, 19-63%)), followed by right-sided lesions (26% (95% CI, 9-43%)). In the majority (68/96 (70.8%)) of instances, pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease genes. The most common (19/96 (19.8%)) monogenic syndrome identified was Kabuki syndrome. CONCLUSIONS: There is an apparent incremental yield of prenatal ES in CHD. While the greatest yield is in CHD associated with ECA, consideration could also be given to performing ES in the presence of an isolated cardiac abnormality. A policy of routine application of ES would require the adoption of robust bioinformatic, clinical and ethical pathways. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Cause of intrauterine and neonatal death in twin pregnancies (CoDiT): development of a novel classification system.

OBJECTIVE: Twin pregnancies have a significantly higher perinatal mortality than singleton pregnancies. Current classification systems for perinatal death lack twin-specific categories, potentially leading to loss of important information regarding cause of death. We introduce and test a classification system designed to assign a cause of death in twin pregnancies (CoDiT). DESIGN: Retrospective cross-sectional study. SETTING: Tertiary maternity unit in England with a perinatal pathology service. POPULATION: Twin pregnancies in the West Midlands affected by fetal or neonatal demise of one or both twins between 1 January 2005 and 31 December 2016 in which postmortem examination was undertaken. METHODS: A multidisciplinary panel designed CoDiT by adapting the most appropriate elements of singleton classification systems. The system was tested by assigning cause of death in 265 fetal and neonatal deaths from 144 twin pregnancies. Cause of death was validated by another obstetrician blinded to the original classification. MAIN OUTCOME MEASURES: Inter-rater, intra-rater, inter-disciplinary agreement and cause of death. RESULTS: Cohen's Kappa demonstrated 'strong' (>0.8) inter-rater, intra-rater and inter-disciplinary agreement (95% CI 0.70-0.91). The commonest cause of death irrespective of chorionicity was the placenta; twin-to-twin transfusion syndrome (TTTS) was the commonest placental cause in monochorionic twins and acute chorioamnionitis in dichorionic twins. CONCLUSIONS: This novel classification system records causes of death in twin pregnancies from postmortem reports with high inter-user agreement. We highlight differences in aetiology of death between monochorionic and dichorionic twins. TWEETABLE ABSTRACT: New classification system for #twin cause of death 'CoDiT' shows high rater agreement.

Prognosis of the co-twin following spontaneous single intrauterine fetal death in twin pregnancies: a systematic review and meta-analysis.

BACKGROUND: Single intrauterine fetal death affects approximately 6% of twin pregnancies and can have serious sequelae for the surviving co-twin. OBJECTIVES: Determine the prognosis of the surviving co-twin following spontaneous single intrauterine fetal death to aid counselling patients and highlight future research areas. SEARCH STRATEGY: Medline, Embase, Web of Science, and Cochrane Library, from 1980 to June 2017. SELECTION CRITERIA: Studies of five or more cases of spontaneous single intrauterine fetal death after 14 weeks gestation, in diamniotic twin pregnancies. DATA COLLECTION AND ANALYSIS: Summary event rates were calculated and stratified by chorionicity. Monochorionic and dichorionic twins, and sub-groups, were compared by odds ratios. MAIN RESULTS: In monochorionic twins, when single intrauterine fetal death occurred at less than 28 weeks' gestation, this significantly increased the rate of co-twin intrauterine fetal death [odds ratio (OR) 2.31, 95% confidence interval (CI) 1.02-5.25, I2  = 0.0%, 12 studies, 184 pregnancies] and neonatal death (OR 2.84, 95% CI 1.18-6.77, I2  = 0.0%, 10 studies, 117 pregnancies) compared with when the single intrauterine fetal death occurred at more than 28 weeks' gestation. Neonatal death in monochorionic twins was significantly higher if the pregnancy was complicated by fetal growth restriction (OR 4.83, 95% CI 1.14-20.47, I2  = 0.0%, six studies, 60 pregnancies) or preterm birth (OR 4.95, 95% CI 1.71-14.30, I2  = 0.0%, 11 studies, 124 pregnancies). Abnormal antenatal brain imaging was reported in 20.0% (95% CI 12.8-31.1, I2  = 21.9%, six studies, 116 pregnancies) of surviving monochorionic co-twins. The studies included in the meta-analysis demonstrated small study effects and possible selection bias. CONCLUSIONS: Preterm birth was the commonest adverse outcome affecting 58.5 and 53.7% of monochorionic and dichorionic twin pregnancies. Outcomes regarding brain imaging and neurodevelopmental comorbidity are an important area for future research, but meta-analysis may be limited due to different methods of assessment. TWEETABLE ABSTRACT: Preterm birth is the highest risk in single co-twin death. Abnormal antenatal brain imaging was found in 1/5 surviving MC twins.

Chlorhexidine vaginal preparation versus standard treatment at caesarean section to reduce endometritis and prevent sepsis-a feasibility study protocol (the PREPS trial).

BACKGROUND: Worldwide caesarean section (CS) delivery is the most common major operation. Approximately 25% of pregnant women undergo a CS in the UK for delivery of their babies. Sepsis and post-natal infection constitute significant maternal mortality and morbidity. Infection following a CS has a number of primary sources including endometritis occurring in 7-17% of women. Sepsis reduction and reduction in antibiotic use have been identified as a national and international priority. The overarching aim of this research is to reduce infectious morbidity from caesarean sections. METHODS: This is a parallel group feasibility randomised controlled trial comparing vaginal cleansing using chlorhexidine gluconate versus no cleansing (standard practice) at CS to reduce infection. Women will be recruited from four National Health Service maternity units. Two hundred fifty women (125 in each arm) undergoing elective or emergency CS, who are aged 16 years and above, and at least 34 weeks pregnant will be randomised. Allocation to treatment will be on a 1:1 ratio. The study includes a qualitative aspect to develop women centred outcomes of wellbeing after delivery. DISCUSSION: The success of the feasibility study will be assessed by criteria related to the feasibility measurements to ascertain if a larger study is feasible in its current format, needs modification or is unfeasible, and includes recruitment, adherence, follow-up and withdrawal measures. TRIAL REGISTRATION: The PREPS trial has been registered with ISRCTN (ISRCTN 33435996).

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

BACKGROUND: 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. OBJECTIVES: Determine accuracy of cffDNA-based NIPT for all conditions. Evaluate influence of other factors on test performance. SEARCH STRATEGY: Medline, Embase, CINAHL, Cochrane Library, from 1997 to April 2015. SELECTION CRITERIA: Cohort studies reporting cffDNA-based NIPT performance in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Bivariate or univariate meta-analysis and subgroup analysis performed to explore influence of test type and population risk. MAIN RESULTS: A total of 117 studies were included that analysed 18 conditions. Bivariate meta-analysis demonstrated sensitivities and specificities, respectively, for: fetal sex, 0.989 (95% CI 0.980-0.994) and 0.996 (95% CI 0.989-0.998), 11 179 tests; rhesus D, 0.993 (95% CI 0.982-0.997) and 0.984 (95% CI 0.964-0.993), 10 290 tests; trisomy 21, 0.994 (95% CI 0.983-0.998) and 0.999 (95% CI 0.999-1.000), 148 344 tests; trisomy 18, 0.977 (95% CI 0.952-0.989) and 0.999 (95% CI 0.998-1.000), 146 940 tests; monosomy X, 0.929 (95% CI 0.741-0.984) and 0.999 (95% CI 0.995-0.999), 6712 tests. Trisomy 13 was analysed by univariate meta-analysis, with a summary sensitivity of 0.906 (95% CI 0.823-0.958) and specificity of 1.00 (95% CI 0.999-0.100), from 134 691 tests. False and inconclusive results were poorly reported across all conditions. Although the test type affected both sensitivity and specificity, there was no evidence that population risk had any effect. CONCLUSION: Performance of cffDNA-based NIPT is affected by condition under investigation. For fetal sex and rhesus D status, NIPT can be considered diagnostic. For trisomy 21, 18, and 13, the lower sensitivity, specificity, and disease prevalence, combined with the biological influence of confined placental mosaicism, designates it a screening test. These factors must be considered when counselling patients and assessing the cost of introduction into routine care. TWEETABLE ABSTRACT: cffDNA NIPT accuracy high, can be diagnostic for fetal sex and rhesus D, but only screening test in aneuploidy.

Comparison of Solomon technique with selective laser ablation for twin-twin transfusion syndrome: a systematic review.

OBJECTIVE: To compare the Solomon and selective techniques for fetoscopic laser ablation (FLA) for the treatment of twin-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies. METHODS: This was a systematic review conducted in accordance with the PRISMA statement. Electronic searches were performed for relevant citations published from inception to September 2014. Selected studies included pregnancies undergoing FLA for TTTS that reported on recurrence of TTTS, occurrence of twin anemia-polycythemia sequence (TAPS) or survival. RESULTS: From 270 possible citations, three studies were included, two cohort studies and one randomized controlled trial (RCT), which directly compared the Solomon and selective techniques for FLA. The odds ratios (OR) of recurrent TTTS when using the Solomon vs the selective technique in the two cohort studies (n = 249) were 0.30 (95% CI, 0.00-4.46) and 0.45 (95% CI, 0.07-2.20). The RCT (n = 274) demonstrated a statistically significant reduction in risk of recurrent TTTS with the Solomon technique (OR, 0.21 (95% CI, 0.04-0.98); P = 0.03). The ORs for the development of TAPS following the Solomon and the selective techniques were 0.20 (95% CI, 0.00-2.46) and 0.61 (95% CI, 0.05-5.53) in the cohort studies and 0.16 (95% CI, 0.05-0.49) in the RCT, with statistically significant differences for the RCT only (P < 0.001). Observational evidence suggested overall better survival with the Solomon technique, which was statistically significant for survival of at least one twin. The RCT did not demonstrate a significant difference in survival between the two techniques, most probably owing to the small sample size and lack of power. CONCLUSION: This systematic review of observational, comparative cohort and RCT data suggests a trend towards a reduction in TAPS and recurrent TTTS and an increase in twin survival, with no increase in the occurrence of complications or adverse events, when using the Solomon compared to the selective technique for the treatment of TTTS. These findings need to be confirmed by an appropriately-powered RCT with long-term neurological follow-up.

Outcome in fetal lower urinary tract obstruction: a prospective registry study.

OBJECTIVE: To describe influences on decision-making and prognostic variables in the prenatal management of fetal lower urinary tract obstruction (LUTO). METHODS: This was a prospective registry study of pregnant women with a male fetus with LUTO from centers within the British Isles and The Netherlands. Women and/or their clinicians were given the treatment option of either conservative management or vesicoamniotic shunting (VAS). Baseline characteristics of women in the registry, reasons for entry to the registry and pregnancy outcomes were assessed. The main study outcomes were survival to 28 days after delivery, further survival to 2 years and renal function. Logistic regression analysis was used to examine prognostic variables that affected outcome. Results were compared with those of women in a randomized controlled trial (RCT) who were allocated randomly to a treatment option. RESULTS: Forty-five women were registered, of whom 78% (35/45) underwent conservative management. Twenty-seven women entered the registry owing to their clinician's preference for management and 18 because of their own preference. Compared to the conservative-management group of the RCT, a higher proportion of women in the registry opting for conservative management had a normal amniotic fluid volume at diagnosis (P = 0.05) and a diagnosis of LUTO ≥ 24 weeks' gestation (P = 0.003). On multivariable logistic regression analysis, these variables showed a significant association with perinatal survival (P < 0.001). Survival to 28 days after delivery was higher in the conservative-management group, at 69% (24/35), compared to 40% (4/10) in the VAS group (P = 0.02) but this difference had limited statistical significance owing to small study size (relative risk, 0.58 (95% CI, 0.26-1.29); P = 0.14). CONCLUSION: In our prospective registry, the majority of fetuses with LUTO received conservative management, which was associated with better short- and long-term outcomes. A significant proportion of these pregnancies had normal amniotic fluid volume and a gestational age at diagnosis of ≥ 24 weeks, characteristics shown to be associated with improved survival.

When is birthweight at term (≥37 weeks' gestation) abnormally low? A systematic review and meta-analysis of the prognostic and predictive ability of current birthweight standards for childhood and adult outcomes.

BACKGROUND: Health outcomes throughout the life course have been linked to fetal growth restriction and low birthweight. A variety of measures exist to define low birthweight, with a lack of consensus regarding which predict adverse outcome. OBJECTIVES: To evaluate the relationship between birthweight standards and childhood and adult outcomes in term-born infants (≥37 weeks' gestation). SEARCH STRATEGY: MEDLINE (1966-January 2011), EMBASE (1980-January 2011), and the Cochrane Library (2011:1) and MEDION were included. SELECTION CRITERIA: Studies comprising live term-born infants (gestation ≥37 completed weeks), with weight or other anthropometric measurements recorded at birth along with childhood and adult outcomes. DATA COLLECTION AND ANALYSIS: Data were extracted to populate 2 × 2 tables relating birthweight standard with outcome, and meta-analysis was performed where possible. MAIN RESULTS: Fifty-nine articles (2 600 383 individuals) were selected. There was no significant relationship between birthweight <2.5 kg (odds ratio [OR] 0.98, 95% confidence intervals [CI] 0.87-1.10) and composite measure of childhood morbidity. Weight <10th centile on the population nomogram showed a small association (OR 1.49, 95% CI 1.02-2.19) for the same outcome. There was no significant association between either of the above measures and adult morbidity. The relationship between other measures and individual outcomes varied. AUTHOR'S CONCLUSIONS: The association between low birthweight, by any definition, and childhood and adult morbidity was inconsistent. None of the current standards of low birthweight was a good predictor of adverse outcome.

Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis.

OBJECTIVES: To assess the effect of timing of folic acid (FA) supplementation during pregnancy on the risk of the neonate being small for gestational age (SGA). DESIGN: A population database study and a systematic review with meta-analysis including the results of this population study. SETTING AND DATA SOURCES: A UK regional database was used for the population study and an electronic literature search (from inception until August 2013) for the systematic review. PARTICIPANTS AND INCLUDED STUDIES: Singleton live births with no known congenital anomalies; 111,736 in population study and 188,796 in systematic review. OUTCOME MEASURES, DATA EXTRACTION AND ANALYSIS: The main outcome was SGA based on customised birthweight centile. Associations are presented as odds ratios (OR) and adjusted odds ratios (aOR), adjusted for maternal and pregnancy-related characteristics. RESULTS: Of 108,525 pregnancies with information about FA supplementation, 92,133 (84.9%) had taken FA during pregnancy. Time of commencement of supplementation was recorded in 39,416 pregnancies, of which FA was commenced before conception in 10,036, (25.5%) cases. Preconception commencement of FA supplementation was associated with reduced risk of SGA <10th centile (aOR 0.80, 95% CI 0.71-0.90, P < 0.01) and SGA <5th centile (aOR 0.78, 95% CI 0.66-0.91, P < 0.01). This result was reproduced when the data were pooled with other studies in the systematic review, showing a significant reduction in SGA (<5th centile) births with preconception commencement of FA (aOR 0.75, 95% CI 0.61-0.92, P < 0.006). In contrast, postconception folate had no significant effect on SGA rates. CONCLUSION: Supplementation with FA significantly reduces the risk of SGA at birth but only if commenced preconceptually independent of other risk factors. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered with PROSPERO number CRD42013004895.

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

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 <10th centile (summary odds ratio [OR] 6.31, 95% confidence interval [95% CI] 4.15-9.58; high-risk population [author definition] n = 6 studies, 28,510 fetuses), and mortality (neonatal death any population summary OR 8.72, 95% CI 2.43-31.26; n = 6 studies, 55,735 fetuses; and perinatal mortality high-risk population summary OR 11.54, 95% CI 4.05-32.9; n = 2 studies, 27;891 fetuses). There was a strong association between polyhydramnios (maximum pool depth >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.

When is birthweight at term abnormally low? A systematic review and meta-analysis of the association and predictive ability of current birthweight standards for neonatal outcomes.

BACKGROUND: Intrauterine growth restriction is a cause of neonatal morbidity and mortality. A variety of definitions of low birthweight are used in clinical practice, with a lack of consensus regarding which definitions best predict adverse outcomes. OBJECTIVES: To evaluate the relationship between birthweight standards and neonatal outcome in term-born infants (at ≥ 37 weeks of gestation). SEARCH STRATEGY: MEDLINE (1966-January 2011), EMBASE (1980-January 2011), and the Cochrane Library (2011:1) and MEDION were included in our search. SELECTION CRITERIA: Studies comprising live term-born infants (gestation ≥ 37 completed weeks), with weight or other anthropometric measurements recorded at birth along with neonatal outcomes. DATA COLLECTION AND ANALYSIS: Data were extracted to populate 2 × 2 tables relating birthweight standard with outcome, and meta-analysis was performed where possible. MAIN RESULTS: Twenty-nine studies including 21 034 114 neonates were selected. Absolute birthweight was strongly associated with mortality, with birthweight < 1.5 kg giving the largest association (OR 48.6, 95% CI 28.62-82.53). When using centile charts, regardless of threshold, the summary odds ratios were significant but closer to 1 than when using absolute birthweight. For all tests, summary predictive ability comprised high specificity and positive likelihood ratio for neonatal death, but low sensitivity and a negative likelihood ratio close to 1. AUTHOR'S CONCLUSIONS: Absolute birthweight is a prognostic factor for neonatal mortality. The indirect evidence suggests that centile charts or other definitions of low birthweight are not as strongly associated with mortality as the absolute birthweight. Further research is required to improve predictive accuracy.

Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis.

BACKGROUND: Approximately 50% of spontaneous miscarriages are associated with chromosome abnormalities. Identification of these karyotypic abnormalities helps to estimate recurrence risks in future pregnancies. Chromosomal microarray analysis (CMA) is transforming clinical cytogenetic practice with its ability to examine the human genome at increasingly high resolution. OBJECTIVES: The aim of this study was to determine whether CMA testing on the products of conception following miscarriage provides better diagnostic information compared with conventional karyotyping. SEARCH STRATEGY: MEDLINE (from 1996 to December 2012), EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012) databases were searched electronically. SELECTION CRITERIA: Studies were selected if CMA was used on products of conception following miscarriage, alongside conventional karyotyping. DATA COLLECTION AND ANALYSIS: Nine papers were included in the systematic review and meta-analysis. All statistical analyses were performed using stata 11.0 (Stata Corp., College Station, TX, USA). MAIN RESULTS: There was agreement between CMA and karyotyping in 86.0% of cases (95% CI 77.0-96.0%). CMA detected 13% (95% CI 8.0-21.0) additional chromosome abnormalities over conventional full karyotyping. In addition, traditional, full karyotyping detected 3% (95% CI 1.0-10.0%) additional abnormalities over CMA. The incidence of a variant of unknown significance (VOUS) being detected was 2% (95% CI 1.0-10.0%). AUTHOR'S CONCLUSIONS: Compared with karyotyping, there appears to be an increased detection rate of chromosomal abnormalities when CMA is used to analyse the products of conception; however, some of these abnormalities are VOUS, and this information should be provided when counselling women following miscarriage and when taking consent for the analysis of miscarriage products by CMA.

The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study and randomised controlled trial: evaluation of the effectiveness, cost-effectiveness and acceptability of percutaneous vesicoamniotic shunting for lower urinary tract obstruction.

BACKGROUND: Congenital lower urinary tract obstruction (LUTO) is a disease associated with high perinatal mortality and childhood morbidity. Fetal vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to improve outcome. OBJECTIVE: To determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO. DESIGN: A multicentre, randomised controlled trial incorporating a prospective registry, decision-analytic health economic model and preplanned Bayesian analysis using elicited opinions. Patient acceptability was evaluated by interview in a qualitative study. SETTING: Fetal medicine departments in the UK, Ireland and the Netherlands. PARTICIPANTS: Pregnant women with a male singleton fetus with LUTO. INTERVENTIONS: In utero percutaneous VAS compared with conservative care. MAIN OUTCOME MEASURES: The primary outcome was survival to 28 days. Secondary outcome measures were survival and renal function at 1 year of age, cost of care and cost per additional life-year and per disability-free survival at the end of 1 year. RESULTS: The trial stopped early with 31 women randomised because of difficulties in recruitment. Of those randomised to VAS and conservative management, 3/16 (19%) and 2/15 (13%), respectively, did not receive their allocated intervention. Based on intention-to-treat analysis, survival at 28 days was higher if allocated VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95% confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44% in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p = 0.25). Neither difference was statistically significant. Of survivors at 1 year, two in the VAS arm had no evidence of renal impairment and four in the VAS arm and two in the conservative arm required medical management. One baby in the conservative arm had end-stage renal failure at 1 year. VAS was more expensive because of additional surgery and intensive care. VAS cost £15,500 per survivor at 1 year and £43,900 per disability-free year. Elicited expert opinions showed uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining elicited opinion with the results, uncertainty of the benefit of VAS remained (RR 1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified visualisation of the fetus during ultrasound scanning, perceiving a personal benefit, and altruism as positive influences on recruitment. Fear of the VAS procedure and the perceived severity of LUTO influenced non-participation. The need for more detailed information about the condition and its implications during pregnancy and following delivery was a further important finding of this research. Recruitment was hampered by logistical and regulatory difficulties, a lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34 (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an associated epidemiological study] and high termination of pregnancy rates. In the registry women also demonstrated a clear preference for conservative management. CONCLUSIONS: Survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially more costly and unlikely to be regarded as cost-effective based on the 1-year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion. The National Institute for Health and Care Excellence interventional procedures guidance (IPG 202) should be updated to reflect this new evidence. Babies in the PLUTO trial should be followed up long term for the different outcomes. TRIAL REGISTRATION: ISRCTN53328556. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further project information.

Systematic review and meta-analysis of middle cerebral artery Doppler to predict perinatal wellbeing.

OBJECTIVE: Identification of the fetus at risk of compromise is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving perinatal outcome. The accuracy of middle cerebral artery (MCA) Doppler for prediction of the fetus at risk of compromise of wellbeing is not known. The objective of this systematic review with bivariate meta-analysis was to evaluate the accuracy of middle cerebral artery Doppler for prediction of compromise of fetal/neonatal wellbeing. STUDY DESIGN: Systematic review and bivariate meta-analysis with searches of Medline, Embase, Cochrane library, Medion (inception to October 2011), hand searching of journal and reference lists, contact with experts. Two reviewers independently selected articles in which the results of middle cerebral artery Doppler were associated with the occurrence of compromise of fetal/neonatal wellbeing. There were no language restrictions applied. RESULTS: Thirty-five studies, testing 4025 fetuses, met the selection criteria. Data were extracted on study characteristics, quality and results to construct 2×2 tables. Likelihood ratios for positive and negative test results, sensitivity, specificity and their 95% confidence intervals were generated for the different indices and thresholds. Meta-analysis showed low predictive accuracy. For prediction of adverse perinatal outcome and perinatal mortality the results were positive likelihood ratios 2.77 (1.93, 3.96) and 1.36 (1.10, 1.67) and negative likelihood ratios 0.58 (0.48, 0.69) and 0.51 (0.29, 0.89) respectively. CONCLUSION: Abnormal middle cerebral artery Doppler showed limited predictive accuracy for compromise of fetal/neonatal wellbeing. High quality primary research or individual patient data meta-analysis looking at this test in combination with other tests is required.

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

OBJECTIVE: To determine the prevalence and outcome of lower urinary tract obstruction (LUTO), including the sensitivity of antenatal diagnosis. DESIGN: A retrospective population-based study. SETTING: Regional population-based congenital anomalies register (WMCAR). POPULATION: Fetuses affected by LUTO delivered between 1995 and 2007 to women resident in the West Midlands. METHODS: Cases were selected from the WMCAR using codes and keyword terms from the International Classification of Diseases, tenth revision (ICD10). Diagnoses were validated using additional data sets from Regional Fetal Medicine, Perinatal Pathology and Paediatric services. MAIN OUTCOME MEASURES: Rates of prevalence, prenatal diagnosis and mortality, with trends. RESULTS: There were 284 LUTO cases in 851 419 births during the study period, representing a total prevalence of 3.34 (2.95-3.72) per 10 000 births, and this prevalence did not change significantly over time. The prevalence of LUTO was significantly higher in Black and minority ethnic groups when compared with white Europeans (OR 2.38; 95% CI 1.87-3.03), and are associated with area-based deprivation measures (P < 0.01). Of all LUTO cases, 221 (77.8%) were isolated, and the remainder were associated with other structural or chromosomal anomalies. The most common subtype was posterior urethral valves (PUVs; n = 179, 63%). In total there were 211 (74.3%) cases of isolated, non-female, singleton fetuses that fitted the referral criteria for in utero vesico-amniotic shunting, giving a prevalence of 2.48 (2.14-2.81) per 10 000 live births. Within this group, the prenatal diagnosis rate was 46.9% (99/211). CONCLUSION: This is the largest population-based study of LUTO that has been performed to date, and provides accurate estimates for prevalence. The low prevalence and relatively low rate of antenatal detection limit the number of cases amenable to prenatal surgical intervention.