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Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. Methods and findings: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster–summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) −6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. Conclusions: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. Trial registration: This trial is registered with the ISRCTN registry, ISRCTN67698474. Matias C Vieira and colleagues evaluate the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age in the DESiGN cluster randomised trial. Why was this study done?: Antenatal detection and appropriate management of small for gestational age (SGA) infants is a recognised strategy to prevent stillbirth; previous reports have suggested the rate of stillbirth is halved when SGA is antenatally detected, compared to undetected SGA. Large observational studies provide conflicting results on the effect of Growth Assessment Protocol (GAP), an antenatal care package, with both findings of increased and no difference in detection of SGA and reduction of stillbirth. The observational nature of all previous studies about GAP limits the assessment of causality in any observed associations. What did the researchers do and find?: To the best of our knowledge, this is the first randomised control trial of GAP, comparing 11,096 births exposed to the intervention (5 clusters) to 13,810 exposed to standard care (6 clusters) during the outcome period. We observed no significant effect on antenatal detection of SGA compared to standard care (25.9% versus 27.7%; adjusted difference 2.2%, 95% confidence interval (CI) −6.4% to 10.7%). The lack of effect should be interpreted in the context of the variable implementation of GAP. What do these findings mean?: This randomised control trial of GAP compared to standard care did not observe improvement in ultrasound detection of SGA; variable implementation of GAP was observed consistent with previous studies. It is imperative that future studies of GAP assess implementation using standardised outcomes (fidelity, reach, and dose), in order to determine generalisability of our findings, identify barriers to implementation, and hence better inform policy for improving perinatal outcomes. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of hospitals in this study limits our ability to study small differences between groups. [ABSTRACT FROM AUTHOR]

Objectives: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. Methods: This was a multicenter cohort study using population‐based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000–2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth‐weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. Results: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3–5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6–18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5‐fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. Conclusions: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Of the 102 women approached, 101 (99%) completed the anxiety thermometer (AnxT). The women were aged between 22–44 years (mean age 34.5 years); about half were primigravida and half multigravida. Almost two-thirds rated their current anxiety as four or above out of a maximum of 10. The most frequently reported concern was health of baby, followed by fears and worries, tiredness, and sleep problems. The high participation rate suggests that the AnxT can be developed to screen anxiety and elicit perinatal and related concerns to facilitate consultation and appropriate triaging. The problem checklist was refined based on the current results. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the natural history and outcome of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancy, according to gestational age at onset and various reported diagnostic criteria, and to quantify the risk of superimposed twin-to-twin transfusion syndrome (TTTS).Methods: This was a cohort study of MCDA twin pregnancies that had their routine antenatal care from the first trimester at St George's Hospital, London, UK. Pregnancies had ultrasound examinations every 2 weeks at 16-24 weeks and then every 2-3 weeks until delivery. The diagnostic criteria for sFGR were estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance ≥ 25%. We also applied other diagnostic criteria reported in a recent Delphi consensus. Pregnancies in which the diagnosis of TTTS was made before that of sFGR were not included in the analysis. Pregnancies that underwent fetal intervention for sFGR were excluded. The incidence of sFGR was compared between the different diagnostic criteria, overall and according to gestational age at onset. In all subsequent analyses, cases of sFGR included those diagnosed according to any of the criteria. The Gratacós classification of sFGR was applied (Type I, II or III). Pregnancy outcomes included miscarriage, intrauterine death, neonatal death and admission to the neonatal unit. Comparisons between groups were carried out using the Mann-Whitney U-test for continuous variables and the chi-square or Fisher's exact test for categorical variables.Results: The analysis included 287 MCDA twin pregnancies. According to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria, the incidence of early (< 24 weeks) sFGR was 4.9%, while that of late sFGR was 3.8%. When applying the various diagnostic criteria, the incidence of early sFGR varied from 1.7% to 9.1% and that of late sFGR varied from 1.1% to 5.9%. In early-onset cases, the incidence of Type I sFGR was 80.8%, that of Type II was 15.4% and that of Type III was 3.8%. The corresponding figures in late-onset cases were 94.4%, 5.6% and 0%. The incidence of superimposed TTTS was 26.9% in cases affected by early-onset sFGR and 5.6% in those affected by late-onset sFGR. The incidence of perinatal death was 8.0% in early-onset sFGR and 5.6% in late-onset sFGR (P = 0.661). Admission to the neonatal unit occurred in 61.0% and 52.9% of cases, respectively (P = 0.484).Conclusions: In MCDA twin pregnancies, early-onset sFGR is slightly more common than is late-onset sFGR, although this difference was not significant, and is associated with worse perinatal outcome. The incidence of Types II and III sFGR is higher in early-onset sFGR. The incidence also varies according to the diagnostic criteria used, which supports the use of standardized international diagnostic criteria. Superimposed TTTS is more common in early- than in late-onset sFGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To report and compare pregnancy outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies with two live fetuses at 11-13 weeks' gestation and to examine the impact of endoscopic laser surgery for severe twin-twin transfusion syndrome (TTTS) and/or selective fetal growth restriction (sFGR) on the outcome of MCDA twins.Methods: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we compared overall survival, fetal loss at < 24 weeks' gestation, perinatal death at ≥ 24 weeks, delivery at < 37 and < 32 weeks, and birth weight < 5th percentile between DC, MCDA and MCMA twins.Results: The study population of 6225 twin pregnancies with two live fetuses at 11-13 weeks' gestation with no major abnormalities included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA twins. In DC twins, the rate of loss at < 24 weeks' gestation in all fetuses was 2.3%; this rate was higher in MCDA twins (7.7%; relative risk (RR), 3.258; 95% CI, 2.706-3.923) and more so in MCMA twins (21.8%; RR, 9.289; 95% CI, 6.377-13.530). In DC twins, the rate of perinatal death at ≥ 24 weeks in all twins that were alive at 24 weeks was 1.0%; this rate was higher in MCDA twins (2.5%; RR, 2.456; 95% CI, 1.779-3.389) and more so in MCMA twins (9.3%; RR, 9.130; 95% CI, 4.584-18.184). In DC twins, the rate of preterm birth at < 37 weeks' gestation in pregnancies with at least one liveborn twin was 48.6%; this rate was higher in MCDA twins (88.5%; RR, 1.824; 95% CI, 1.760-1.890) and more so in MCMA twins (100%; RR, 2.060; 95% CI, 2.000-2.121). In DC twins, the rate of preterm birth at < 32 weeks was 7.4%; this rate was higher in MCDA twins (14.2%; RR, 1.920; 95% CI, 1.616-2.281) and more so in MCMA twins (26.8%; RR, 3.637; 95% CI, 2.172-6.089). In DC twin pregnancies with at least one liveborn twin, the rate of a small-for-gestational-age neonate among all liveborn twins was 31.2% and in MCDA twins this rate was higher (37.8%; RR, 1.209; 95% CI, 1.138-1.284); in MCMA twins, the rate was not significantly different (33.3%; RR, 1.067; 95% CI, 0.783-1.455). Kaplan-Meier analysis showed a significant difference in survival in MCDA and MCMA twins, compared to DC twins, for both the interval of 12 to < 24 weeks' gestation (log-rank test, P < 0.0001 for both) and that of ≥ 24 to 38 weeks (log-rank test, P < 0.0001 for both). Endoscopic laser ablation of intertwin communicating placental vessels was carried out in 127 (10.0%) MCDA twin pregnancies for TTTS and/or sFGR and, in 111 of these, surgery was performed at < 24 weeks; both fetuses survived in 62 (55.9%) cases, one fetus survived in 25 (22.5%) cases and there were no survivors in 24 (21.6%) cases. On the extreme assumption that, had laser surgery not been carried out in these cases, all fetuses would have died, the total fetal loss rate at < 24 weeks' gestation in MCDA twins would have been 13.5%.Conclusions: The rates of fetal loss at < 24 weeks' gestation, perinatal death at ≥ 24 weeks and preterm birth are higher in MCDA and more so in MCMA twins than in DC twins. In MCDA twins, the rate of fetal loss may have been reduced by endoscopic laser surgery in those that developed early TTTS and/or sFGR. These data would be useful in counseling parents as to the likely outcome of their pregnancy and in defining strategies for surveillance and interventions in the management of the different types of twin pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. Design: Population‐based pregnancy cohort. Setting: Medical records (CPRD‐GOLD) from England. Population: 417 028 pregnancies during 1998–2014. Methods: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. Main outcome measures: NVP/HG diagnoses, treatments, and hospital admissions. Results: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998–2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first‐line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first‐line, 9% second‐line, 1% third‐line treatment). Conclusion: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions. The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies.Methods: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013.Results: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation.Conclusions: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between weight discordance and neonatal morbidity in twin pregnancy progressing to at least 34 weeks of gestation. The secondary aim was to determine the predictive accuracy of different weight discordance cut-offs in predicting neonatal morbidity in twin pregnancy.Methods: This was a retrospective multicenter cohort study of all twin pregnancies booked for antenatal care at four hospitals in the Southwest Thames region of London Obstetric Research Collaborative (STORK) over a period of 10 years. Ultrasound data were obtained by a search of each hospital's obstetric ultrasound computer database, while outcome details were obtained from the computerized maternity and neonatal records. The primary outcome was incidence of composite neonatal morbidity in twin pregnancy with birth-weight discordance. Logistic regression was used to identify and adjust for potential confounders, while a receiver-operating characteristics (ROC) curve was used to determine predictive accuracy.Results: Nine hundred and thirty-nine twin pregnancies (760 dichorionic, 179 monochorionic) were included. Gestational age at birth and birth-weight decile were significantly lower in pregnancies complicated by neonatal morbidity compared with those which were not (P < 0.001 for both). On multivariable logistic regression analysis, gestational age at birth (P < 0.001), birth-weight decile (P = 0.029) and birth-weight discordance (P = 0.019), but not chorionicity (P = 0.477) or presence of at least one small-for-gestational-age (SGA) twin (P = 0.245), were associated independently with the risk of neonatal morbidity. There was a progressive increase in the risk of neonatal morbidity with increasing birth-weight discordance. Despite this association, birth-weight discordance showed an overall poor predictive accuracy for neonatal morbidity, with an area under the ROC curve of 0.58 (95% CI, 0.53-0.63) with an optimal cut-off of 17.6%, showing sensitivity and specificity of 35.2% (95% CI, 27.8-43.2%) and 83.2% (95% CI, 80.4-85.8%), respectively.Conclusion: Intertwin birth-weight discordance is associated independently with the risk of neonatal morbidity in twins born after 34 weeks' gestation, irrespective of chorionicity or diagnosis of SGA in either twin. However, its predictive accuracy for neonatal morbidity is poor. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine the gestational age at delivery in dichorionic (DC) and monochorionic (MC) twin pregnancies, with and without pre-eclampsia (PE), and to determine the relative risk of total and preterm PE compared with that in singleton pregnancies.Methods: This was a screening study for PE in twin pregnancies undergoing first-trimester combined screening for aneuploidy and subsequently delivering two phenotypically normal live or stillborn babies at ≥ 24 weeks' gestation. The distribution of gestational age at delivery in DC and MC twins was determined and compared with that in singleton pregnancies from the same population. The relative risk for total and preterm PE in twins compared with singleton pregnancies was determined. Kaplan-Meier estimates of the cumulative incidence of PE in twin and singleton pregnancies, assuming no other cause for delivery, were determined and hazard ratios for twins relative to singletons were obtained from a Cox proportional hazards regression model.Results: The incidence of PE in singletons was 2.3% (2162/93 297), in DC twin pregnancies was 8.1% (145/1789) and in MC twin pregnancies was 6.0% (26/430). Compared with singletons, the relative risk of total PE was 3.5 for DC twins and 2.6 for MC twins. Delivery < 37 weeks' gestation occurred in 5.5% of singletons, 46.5% of DC twins and 91.4% of MC twins. The incidence of preterm PE was 0.6%, 5.5% and 5.8% for singletons, DC twins and MC twins, respectively. Compared with singletons, the relative risk of preterm PE was 8.7 for DC twins and 9.1 for MC twins. In the Cox proportional hazards regression model, the hazard ratios for DC and MC twin pregnancies relative to singleton pregnancies were 14 and 23, respectively.Conclusions: The relative risk of preterm PE in DC and MC twins is similar and substantially higher than in singleton pregnancies. In ongoing twin pregnancies, the high relative risk of PE may merit a higher intensity of monitoring than is routine for singleton pregnancies. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relation between first-trimester fetal growth discrepancy, as assessed by crown-rump length (CRL) at 11+0 to 13+6 weeks of gestation, and subsequent development of preeclampsia (PE) in dichorionic diamniotic (DCDA) twin pregnancies. The association between inter-twin CRL and birth weight (BW) discrepancy was also investigated. Methods: This was a retrospective, case-control study of DCDA twin pregnancies. Inter-twin CRL discrepancy was calculated as 100×(larger CRL-smaller CRL)/larger CRL. BW discordance was calculated as 100×(larger BW-smaller BW)/larger BW. Results: The study included 299 DCDA pregnancies that remained normotensive and 35 that subsequently developed PE. There was no significant difference in the inter-twin CRL discrepancy between pregnancies complicated by PE and those that were not [3.2%, interquartile range (IQR): 0.5-4.5% vs. 3.3%, IQR: 1.4-5.5%; P=0.17]. There was a positive correlation between inter-twin CRL and BW discrepancy but only in pregnancies that remained normotensive (P<0.001). In women that subsequently developed PE, there was no association between inter-twin CRL and BW discordance (P=0.54). Conclusions: In unselected DCDA twins, first-trimester CRL discrepancy is not different between pregnancies that subsequently develop PE and those that remain normotensive. Furthermore, in pregnancies that are complicated by PE, the association between inter-twin CRL and BW discrepancy appears to be lost. [ABSTRACT FROM AUTHOR]

Background The number of twins born in Australia steadily increased from 2420 sets in 1983 to 4458 sets in 2010. At one stage, almost 25% of all twin deliveries in Australia were a consequence of assisted reproductive technologies. Aims To determine the influence of a policy of single embryo transfer (SET) on the rate of multiple deliveries in Australia. Methods We used population data to compare the prevalence of twin and higher order multiple births in women giving birth in Australia before and after the implementation of the RTAC COP 2001 and 2005 revisions for ART units. Results There was a steady fall in the twin delivery rate for assisted reproductive technologies from 210.4 per 1000 deliveries in 2001 to 84.3 per 1000 deliveries in 2009. In 2009, assisted reproductive technologies accounted for approximately 16% of all twin births from 3% of all conceptions, substantially less than the 24.5% in 2002. Conclusions The decline in multiple births is multifactorial. However, the fall in the proportion of ART multiple births has paralleled adoption of a voluntary policy of SET within a setting of largely public funding of ART. [ABSTRACT FROM AUTHOR]

Background To investigate the indications for offering selective fetal reduction in monochorionic (MC) and dichorionic (DC) twins and to correlate obstetric outcome with the antenatal procedure. Methods All cases of MC and DC twins discordant for structural anomalies and for chromosomal/genetic abnormalities were included. Selective reductions performed for twin-to-twin transfusion syndrome or growth restriction were excluded. For DC twins, feticide was achieved using intracardiac injection of potassium chloride ( KCl). For MC twins, bipolar cord occlusion ( BCO), interstitial laser or radiofrequency ablation ( RFA) was used. Results There were 121 twin pregnancies discordant for structural and chromosomal abnormalities. Only 88 (56 were MC twins and 32 were DC twins) had selective reduction. For both MC and DC twins, the leading indication for selective reduction was structural anomalies with CNS malformations the most common. For all MC fetal reduction techniques, the overall pregnancy loss rate (<24 weeks) was 8.9% with RFA having the lowest procedure loss rate (7.7%). The preterm delivery rate was lowest with reduction in DC pregnancies. The live birth rates for MC twins were >87% and 100% for DC twins. Conclusions Selective reduction in MC pregnancies carries an increased procedure-related and preterm delivery rate compared with DC pregnancies. The main indication for selective reduction was structural malformations, with a predominance of CNS anomalies. [ABSTRACT FROM AUTHOR]

The article presents a study on the association between crown-rump length (CRL) discrepancy and fetal loss, chorionicity, and birth-weight discordance in 507 twin pregnancies in England. The study used Mann-Whitney U-test, chi-square test, and Kolmogorov test to calculate and analyze CL discrepancy and birth-weight differences and discordance. Results show that fetal loss is prevalent among monochorionic twins while birth weight problem is related to dichorionic twins with CRL discrepancy.

Background: Congenital anomalies are more common in twins than singletons but in the majority, aetiology is not known. Our aim was to test the hypothesis that survivors of an early loss in a multiple conception, compared with all singletons, are at increased risk of congenital anomaly.Methods: Data were abstracted from the UK population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey, 1998-2004.Results: Among 3311 twin conceptions, both conceptuses were lost at <16 weeks gestation in 67, and one conceptus in 142 conceptions. Of the 142 singleton survivors, two died in infancy, two were terminated for a congenital anomaly and 11 of 138 had a congenital anomaly (prevalence 915.5 per 10,000 births). There were 197 congenital anomalies among 5948 registered twin births (331.2 per 10,000). The relative risk (RR) of congenital anomalies in a singleton with early loss of a conceptus and twins was 2.40 [95% confidence interval (CI): 1.34-4.29]. There were 4265 infants with a congenital anomaly among the 206 914 singletons [206.1 per 10,000 births: RR twin:singleton 1.61 (95% CI 1.40-1.89)].Conclusions: A highly significant increase in the risk of congenital anomaly in survivors from a multiple conception following early loss of a conceptus supports the hypothesis that many congenital anomalies are associated with monozygotic multiple conceptions. [ABSTRACT FROM AUTHOR]

After a long continuous decrease, the twinning and higher multifetal rates in many developed countries have increased during the last 2 to 3 decades. This change has been attributed to delayed childbearing and to increased use of subfertility treatments, particularly in women over 35 years of age. In this study we analyze how these new trends depend on changes in the effect of maternal age on the rates of multiple maternities. Our study is based on data for England and Wales for the period 1938 to 2003. The temporal variations show a decreasing trend to a trough around 1980 and after that a steady increase. This increase was more marked for higher multifetal rates and was particularly high for quadruplets. Furthermore, we identified changes in the age-specific rates resulting in increased levels for older mothers. These findings are in good agreement with our results from Nordic populations. [ABSTRACT FROM AUTHOR]

Fetal death in a twin conception during second and third trimester is associated with increased risk of cerebral injury in the surviving twin. The aim of this study is to test the hypothesis that even early fetal losses as a 'vanishing' twin may be associated with an increased risk of cerebral impairment in the surviving twin. The study population comprised 362 pregnant women attending Liverpool Women's Hospital recruited between 1999 and 2001. Women were classified according to the first ultrasound scan into 3 groups: vanishing twin, twin and singleton. The vanishing twin group was further subdivided into 'definite' and 'probable'. Children from these pregnancies were assessed at 1 year of age for their development and neurological function using the Griffiths Mental and Developmental Scales and Optimality score. Children from 229 pregnancies (63.2%) attended the assessment. Information on children from a further 21 (5.8%) pregnancies was obtained through a review of hospital records. Cerebral impairment was found in 2 children from the vanishing twin group, 2 from the twin group and none from the singleton group. When cases with definite vanishing twin are considered there is a significant difference between the vanishing twin and singleton group (relative risk 6.1; 95% confidence interval 1.5-8.3; p = .03). An additional study with an increased sample size would enable a more robust conclusion. [ABSTRACT FROM AUTHOR]

Selective abortion was shown to be increasingly common in England and Wales over a 9-year period, occurring most frequently as twin to singleton reductions in the 1st trimester. We analysed the trends in selective abortion (SA) in multiple pregnancies in England and Wales between 2009 and 2018. This is a cross-sectional study looking at 1143 women with multiple pregnancies in England and Wales undergoing SA. There were a total of 1143 cases of SA between 2009 and 2018 in England and Wales, representing 0.07% of total abortions. There has been a steady increase in cases, from 90 in 2009 to 131 in 2018, with 82.3% justified under ground E of The Abortion Act 1967. The majority of SAs were carried out at 13-19 weeks gestation, and intracardiac injection of potassium chloride was the most prevalent method (75%). Twin to singleton reductions accounted for 59%, the most common form of SAs. Over half of all cases (59%) were performed in women aged 30-39 years, and 84% of all women were of White ethnicity. SA has been an option available for couples diagnosed with multiple pregnancy, especially when there are discordant anomalies. Although SA may decrease multiple pregnancy-related complications, preventative methods must be championed., (© 2021. The Author(s).)

Background: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies.Objective: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance.Study Design: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020.Results: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%.Conclusion: This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins. [ABSTRACT FROM AUTHOR]

During the 1960s and 1970s, the maternal age-specific twinning rates were declining in England and Wales and many other countries. However, around 1980 this change reversed and since then twinning rates have been increasing. The question arises whether this increase is simply a consequence of hormonal induction of ovulation and various other techniques of assisted reproduction. The question assumes some importance because the level of ‘natural’ twinning may be an index of reproductive (and other) health. Nationwide data on the prevalence of medically assisted conceptions are not available, so indirect methods have to be used to answer the question. It is tentatively concluded here that the ‘natural’ twinning rate has recently been increasing in England and Wales and Belgium. These conclusions are based on two assumptions: (i) that in England and Wales, conceptions by young women are infrequently preceded by medical assistance; and (ii) in Belgium, the rate of medically assisted conceptions is not lower in East Flanders than in the rest of Belgium. Direct data on these points would test these conclusions. [ABSTRACT FROM PUBLISHER]

Examines the levels of maternal serum α-Fetoprotein (AFP) in multiple pregnancies in Oxford, England. Correlation of high levels of AFP with anencephaly and spina bifida; Sources of the increased maternal serum AFP in pregnant women; Increase in AFP levels in multiple pregnancies.

Examines the diagnosis of multiple pregnancy in London, England. Performance of ultrasonography in the presence of a twin pregnancy; Association of increased perinatal death with twin pregnancy; Importance of early diagnosis on multiple pregnancy.