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.

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.

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.

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.

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.

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 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.

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.

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.

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

OBJECTIVE: To determine the effectiveness of fetal cystoscopy in the prenatal diagnosis of and intervention for congenital lower urinary tract obstruction. METHODS: This study was a literature search using MEDLINE, Embase, Cochrane Library, MEDION, Web of Science reference lists and contact with experts. All studies reporting on fetal cystoscopy in lower urinary tract obstruction with data for a 2 × 2 table were selected for review. No language restrictions were applied. There was independent selection of studies, data extraction and quality assessment by two reviewers. Peto odds ratios were calculated as a summary measure of effect. RESULTS: A total of 2071 citations were identified and 66 papers selected for detailed evaluation, from which four papers with a total of 63 patients were selected for inclusion. Two papers had results for the use of cystoscopy in diagnosis, showing that fetal cystoscopy altered the ultrasound diagnosis of the underlying pathology in 36.4 and 25.0% of fetuses, respectively. Compared to no treatment, fetal cystoscopic intervention demonstrated an odds ratio for improved perinatal survival of 20.51 (95% CI, 3.87-108.69). However, comparing vesicoamniotic shunt (VAS) with fetal cystoscopy there appeared to be no significant improvement in the perinatal survival odds ratio of 1.49 (95% CI, 0.13-16.97). These results had wide CIs and for cystoscopy vs. VAS, all results crossed the line of no effect. CONCLUSION: There is little published evidence for the effectiveness of therapeutic fetal cystoscopy as an intervention for congenital lower urinary tract obstruction and the quality of this evidence is poor. It should thus be considered to be an 'experimental intervention' and subjected to further investigation.

Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high-risk population: systematic review and bivariate meta-analysis.

OBJECTIVE: We investigated the accuracy of fetal umbilical artery Doppler to predict the risk of compromise of fetal/neonatal wellbeing in a high-risk population. METHODS: Searches in MEDLINE, Embase, The Cochrane Library and Medion (from inception to March 2009) were carried out, together with hand searching of relevant journals, reference list checking of included articles and contact with experts. Criteria for selection were observational studies with umbilical artery Doppler used in a high-risk pregnant population with an outcome measure for compromise of fetal/neonatal wellbeing. Data on study design, quality and results were extracted to construct 2 × 2 tables. Bivariate meta-analysis was performed. Likelihood ratios (LRs) were used as the summary measure of accuracy. RESULTS: One-hundred and four studies met the selection criteria (19 191 fetuses). In a high-risk population, umbilical artery Doppler predicted small-for-gestational age with a pooled LR+ of 3.76 (2.96, 4.76) and pooled LR- of 0.52 (0.45, 0.61), and compromise of fetal/neonatal wellbeing with a pooled LR+ of 3.41 (2.68, 4.34) and pooled LR- of 0.55 (0.48, 0.62). In this group it was also possible to predict, with accuracy, intrauterine death (pooled LR+ = 4.37 (0.88, 21.8); pooled LR- = 0.25 (0.07, 0.91)) and acidosis (pooled LR+ = 2.75 (1.48, 5.11); pooled LR- = 0.58 (0.36, 0.94)). CONCLUSIONS: In a high-risk population, fetal umbilical artery Doppler is a moderately useful test with which to predict mortality and risk of compromise.

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.

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

OBJECTIVE: To evaluate the effects of operator experience on perinatal outcome in a single centre. DESIGN: Prospective consecutive cohort study. SETTING: Regional tertiary referral Fetal Medicine Centre in the UK. POPULATION: Pregnant women with monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome (TTTS) (at ≤26 completed weeks of gestatiuon) treated by fetoscopic laser coagulation (FLC) between October 2004 and November 2009. METHODS: Pregnancy characteristics and outcomes were collected. Logistic regression analysis was employed to determine the effect of a priori defined variables on outcome. MAIN OUTCOME MEASURE: Perinatal survival (survival to 28 days or beyond) for one or more twins. RESULTS: There were 164 consecutive sets of monochorionic twins. The median gestational age (GA) at FLC was 20.4 weeks (interquartile range 18-22.1 weeks), the median interval from FLC to delivery was 88.5 days (interquartile range 53-101 days) and the median GA at delivery was 33.2 weeks (interquartile range 29.7-34.9 weeks). The overall survival was 62%; perinatal survival of one or more twins was 85%. These outcomes improved after about 61 procedures were performed, and after about 3.4 years of experience. Univariate logistic regression analysis indicated that Quintero stage-IV disease decreased (OR 0.26; 95% CI 0.10-0.69) and prolongation of GA at delivery increased the survival of the twins (OR 1.34; 95% CI 1.12-1.60) (P < 0.01). Increasing experience of the procedure by operator led to a significant increase in perinatal survival (P < 0.01; OR 4.59; 95% CI 1.84-11.44). Multivariate logistic regression analysis indicated that only GA at delivery increased survival overall (OR 1.34; 95% CI 1.12-1.60; P = 0.01). CONCLUSIONS: These data indicate that both relatively large numbers treated and experience with FLC minimises any adverse outcome in monochorionic pregnancies with severe TTTS.

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

BACKGROUND: Congenital lower urinary tract obstruction is associated with high mortality and morbidity. Antenatal detection has improved with advances in ultrasound technology, and has allowed the option of antenatal intervention. OBJECTIVES: To systematically review the literature to evaluate the effectiveness of antenatal interventions to improve perinatal survival and postnatal renal function in congenital lower urinary tract obstruction. SEARCH STRATEGY: Extensive electronic searches (database inception 2009) using Medical Subject Headings (MeSH) and keywords, without restrictions. Reference lists of included studies were checked, and all authors were contacted. SELECTION CRITERIA: Studies were selected according to a predefined protocol. The included studies were observational or randomised trials, where an intervention was performed in utero to treat congenital lower urinary tract obstruction, compared with another intervention or no treatment. DATA COLLECTION AND ANALYSIS: Data were extracted on study design, quality and results to construct 2 x 2 tables. Meta-analysis was performed where possible. Peto ORs with 95% CIs were computed. MAIN RESULTS: Prenatal bladder drainage improved perinatal survival compared with no treatment (OR 3.86, 95% CI 2.00-7.45). This effect was amplified in a subgroup with poor predicted prognosis (OR 12.85, 95% CI 1.25-153.03). However, although treatment increases survival, it appears that the residual risk of poor long-term postnatal renal function is uncertain (OR 0.50, 95% CI 0.13-1.90). AUTHOR'S CONCLUSIONS: Antenatal bladder drainage appears to improve perinatal survival in cases of congenital lower urinary tract obstruction, but may confer a high residual risk of poor postnatal renal function, based on observational studies. Randomised research with long-term follow up is necessary to determine the role of antenatal treatment in clinical practice.

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. OBJECTIVE: To evaluate the accuracy of antenatal ultrasound in the prediction of postnatal renal function in cases of congenital lower urinary tract obstruction (LUTO). SEARCH STRATEGY: We conducted electronic searches in MEDLINE, EMBASE, the Cochrane Library, MEDION, SIGLE, SCISEARCH Index of scientific and technical proceedings, National Research Register (database inception - 2008) and Medical Conferences register and searched reference lists. SELECTION CRITERIA: Two reviewers independently selected articles in which the accuracy of fetal ultrasound features were evaluated to predict postnatal renal function with no language restrictions. DATA COLLECTION AND ANALYSIS: Data were extracted on study characteristics, quality and results to construct 2 x 2 tables. Likelihood ratios for positive (LR+) and negative (LR-) test results, sensitivity and specificity were generated for the different ultrasound parameters and reference standards. MAIN RESULTS: Thirteen articles that met the selection criteria, including 215 women and 33 2 x 2 tables. Meta-analysis was performed using clinically similar subgroups to minimise clinical heterogeneity. The ultrasound parameter that showed the best predictive value for postnatal renal function in survivors was renal cortical appearance, sensitivity 0.57 (95% CI 0.37-0.76) and specificity 0.84 (95% CI 0.71-0.94), area under the curve 0.78. CONCLUSION: Measurement of amniotic fluid volume and the appearance of the renal cortex at diagnosis of LUTO show promising predictive accuracy for poor postnatal renal function.