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.