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Objectives: Twin pregnancies are at higher risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a major cause of perinatal mortality, but its impact on twins vs singletons remains unclear. The primary objective of this study was to investigate the association of FGR and small-for-gestational age (SGA) with stillbirth in twin compared with singleton pregnancies. A secondary objective was to assess these associations stratified by gestational age at delivery. Furthermore, we aimed to compare the associations of FGR and SGA with stillbirth in twin pregnancies using twin-specific vs singleton birth-weight charts, stratified by chorionicity., Methods: This was a retrospective cross-sectional study of pregnancies receiving obstetric care and giving birth between 1999 and 2022 at St George's Hospital, London, UK. The exclusion criteria included triplet and higher-order pregnancies, those resulting in miscarriage or live birth at ≤ 23 + 6 weeks, termination of pregnancy and missing data regarding birth weight or gestational age at birth. Birth-weight data were collected and FGR and SGA were defined as birth weight <5 th and <10 th centiles, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA with stillbirth in twin pregnancies was investigated using mixed-effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for intertwin dependency. Analyses were stratified by gestational age at delivery and chorionicity. Statistical significance was set at P ≤ 0.001., Results: The study included 95 342 singleton and 3576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). SGA and FGR were associated significantly with stillbirth in singleton pregnancies across all gestational ages at delivery: the odds ratios (ORs) for SGA and FGR were 2.36 ((95% CI, 1.78-3.13), P < 0.001) and 2.67 ((95% CI, 2.02-3.55), P < 0.001), respectively, for delivery before 32 weeks; 2.70 ((95% CI, 1.71-4.31), P < 0.001) and 2.82 ((95% CI, 1.78-4.47), P < 0.001), respectively, for delivery between 32 and 36 weeks; and 3.85 ((95% CI, 2.83-5.21), P < 0.001) and 4.43 ((95% CI, 3.16-6.12), P < 0.001), respectively, for delivery after 36 weeks. In twin pregnancies, when stratified by gestational age at delivery, both SGA and FGR determined by twin-specific birth-weight charts were associated with increased odds of stillbirth for those delivered before 32 weeks (SGA: OR, 3.87 (95% CI, 1.56-9.50), P = 0.003 and FGR: OR, 5.26 (95% CI, 2.11-13.01), P = 0.001), those delivered between 32 and 36 weeks (SGA: OR, 6.67 (95% CI, 2.11-20.41), P = 0.001 and FGR: OR, 9.54 (95% CI, 3.01-29.40), P < 0.001) and those delivered beyond 36 weeks (SGA: OR, 12.68 (95% CI, 2.47-58.15), P = 0.001 and FGR: OR, 23.84 (95% CI, 4.62-110.25), P < 0.001). However, the association of stillbirth with SGA and FGR in twin pregnancies was non-significant when diagnosis was based on singleton charts (before 32 weeks: SGA, P = 0.014 and FGR, P = 0.005; 32-36 weeks: SGA, P = 0.036 and FGR, P = 0.008; after 36 weeks: SGA, P = 0.080 and FGR, P = 0.063)., Conclusion: Our study demonstrates that SGA and, especially, FGR are associated significantly with an increased risk of stillbirth across all gestational ages in singleton pregnancies, and in twin pregnancies when twin-specific birth-weight charts are used. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Pregnancies with fetal growth restriction (FGR) are at increased risk for pre-eclampsia. Angiogenic markers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre-eclampsia in growth-restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre-eclampsia in pregnancies with FGR and suspected pre-eclampsia., Methods: This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt-1 and PlGF for suspicion of pre-eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre-eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre-eclampsia at various timepoints., Results: In this cohort of 93 women, pre-eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt-1/PlGF ratio consistently showed a stronger association with the development of pre-eclampsia compared to sFlt-1 or PlGF alone (pre-eclampsia within 1 week: area under the receiver-operating-characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt-1/PlGF ratio were associated more strongly with pre-eclampsia hazard compared to models including sFlt-1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt-1/PlGF ratio decreased after the 2-week timepoint. The established cut-off value for the sFlt-1/PlGF ratio of < 38 was effective for ruling out pre-eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952., Conclusions: Use of the sFlt-1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre-eclampsia in pregnancies with FGR. Established cut-offs for ruling out the development of pre-eclampsia in the short term seem to be effective in these patients. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Fetal growth restriction contributes to the excess perinatal mortality and morbidity associated with twin pregnancies. Regular ultrasound monitoring for fetal growth restriction is an essential component of antenatal care of twin gestations. It is accepted that twins have divergent growth trajectories around 28-30 weeks' gestation and are born smaller compared to singletons. Despite this well-established difference in fetal growth, twin pregnancies have been traditionally managed using growth standards developed for singleton pregnancies. Numerous recent studies have demonstrated a strong case supporting the use of twin-specific growth standards, but clinical implementation has been lacking. In this paper, we will review the evidence on factors affecting fetal growth, the rationale for twin-specific reference charts, clinical evidence for their use, and future direction of research. Applying singleton growth standards to twin pregnancies inflates the abnormal growth rate, and recent clinical evidence from several studies suggests that they are too stringent for classification of twins. The association of adverse perinatal and maternal outcomes such as perinatal death, preterm birth, neonatal care unit admission, hypertensive disorders of pregnancy, and composite neonatal morbidity is stronger when classification is made using twin-specific standards compared to singletons., Competing Interests: Conflict of interest The authors have no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR)., Methods: This was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin-twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV-PIV) were converted to Z-scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin., Results: We analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type-I and 38 (36.5%) with Type-II sFGR at initial presentation. In pregnancies complicated by Type-II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type-I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type-II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth-weight centile of the smaller twin (P < 0.01), those with Type-I sFGR had earlier GA at delivery (P = 0.007) and those with Type-II sFGR had higher DV-PIV Z-score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56-0.88); P = 0.002), Type-II sFGR (HR, 3.53 (95% CI, 1.37-9.07); P = 0.008) and higher DV-PIV Z-score (HR, 1.36 (95% CI, 1.12-1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin., Conclusions: Pregnancies complicated by Type-II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type-I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR. Earlier GA at diagnosis, Type-II sFGR and higher DV-PIV Z-score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Purpose of Review: Two-thirds of the pregnancies complicated by stillbirth demonstrate growth restriction. Identification of the foetus at risk of growth restriction is essential to reduce the risk of stillbirth. The aim of this review is to critically appraise the current evidence regarding clinical utility of cerebroplacental ratio (CPR) in antenatal surveillance., Recent Findings: The CPR has emerged as an assessment tool for foetuses at increased risk of growth disorders. CPR is a better predictor of adverse events compared with middle-cerebral artery or umbilical artery Doppler alone. The predictive value of CPR for adverse perinatal outcomes is better for suspected small-for-gestational age foetuses compared with appropriate-for-gestational age (AGA) foetuses. CPR could be useful for the risk stratification of small-for-gestational age foetuses to determine the timing of delivery and also to calculate the risk of intrapartum compromise or prolonged admission to the neonatal care unit. Although there are many proposed cut-offs for an abnormal CPR value, evidence is currently lacking to suggest the use of one cut-off over another. CPR appears to be associated with increased risk of intrapartum foetal compromise, abnormal growth velocity, and lower birthweight in AGA foetuses as well. Moreover, birthweight differences are better explained with CPR compared to other factors such as ethnicity. However, the role of CPR in predicting adverse perinatal outcomes such as acidosis or low Apgar scores in AGA foetuses is yet to be determined., Summary: CPR appears to be a useful surrogate of suboptimal foetal growth and intrauterine hypoxia and it is associated with a variety of perinatal adverse events.

Objective: The use of twin-specific vs singleton growth charts in the assessment of twin pregnancy has been controversial. The aim of this study was to assess whether a diagnosis of small-for-gestational age (SGA) made using twin-specific estimated-fetal-weight (EFW) and birth-weight (BW) charts is associated more strongly with adverse neonatal outcomes in twin pregnancies, compared with when the diagnosis is made using singleton charts.Methods: This was a cohort study of twin pregnancies delivered at St George's Hospital, London, between January 2007 and May 2020. Twin pregnancies complicated by intrauterine death of one or both twins, fetal aneuploidy or major abnormality, twin-twin transfusion syndrome or twin anemia-polycythemia sequence and those delivered before 32 weeks' gestation, were excluded. SGA was defined as EFW or BW below the 10th centile, and was assessed using both twin-specific and singleton EFW and BW charts. The main study outcome was composite adverse neonatal outcome. Mixed-effects logistic regression analysis with random pregnancy-level intercepts was used to test the association between SGA classified using the different charts and adverse neonatal outcome.Results: A total of 1329 twin pregnancies were identified, of which 913 (1826 infants) were included in the analysis. Of these pregnancies, 723 (79.2%) were dichorionic and 190 (20.8%) were monochorionic. Using the singleton charts, 33.3% and 35.7% of pregnancies were classified as SGA based on EFW and BW, respectively. The corresponding values were 5.9% and 5.6% when using the twin-specific charts. Classification as SGA based on EFW using the twin charts was associated significantly with composite adverse neonatal outcome (odds ratio (OR), 4.78 (95% CI, 1.47-14.7); P = 0.007), as compared with classification as appropriate-for-gestational age (AGA). However, classification as SGA based on EFW using the singleton standard was not associated significantly with composite adverse neonatal outcome (OR, 1.36 (95% CI, 0.63-2.88); P = 0.424). Classification as SGA based on EFW using twin-specific standards provided a significantly better model fit than did using the singleton standard (likelihood ratio test, P < 0.001). When twin-specific charts were used, classification as SGA based on BW was associated significantly with a 9.3 times increased odds of composite adverse neonatal outcome (OR, 9.27 (95% CI, 2.86-30.0); P < 0.001). Neonates classified as SGA according to the singleton BW standard but not according to the twin-specific BW standards had a significantly lower rate of composite adverse neonatal outcome than did AGA twins (OR, 0.24 (95% CI, 0.07-0.66); P = 0.009).Conclusions: The singleton charts classified one-third of twins as SGA, both prenatally and postnatally. Infants classified as SGA according to the twin-specific charts, but not those classified as SGA according to the singleton charts, had a significantly increased risk of adverse neonatal outcome compared with infants classified as AGA. This study provides further evidence that twin-specific charts perform better than do singleton charts in the prediction of adverse neonatal outcome in twin pregnancies. The use of these charts may reduce misclassification of twins as SGA and improve identification of those that are truly growth restricted. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Twin pregnancy is associated with a 2-3-fold increased risk of stillbirth compared with singleton pregnancy. Despite the fact that the growth pattern in twins has been shown to be different from that in singletons, it is controversial whether twin-specific growth charts should be used routinely. A major goal of prenatal ultrasound is to identify fetuses with growth restriction at risk of stillbirth. The main aim of this study was to compare the performance of chorionicity-specific twin charts with singleton charts, both customized and non-customized, in the antenatal prediction of small-for-gestational-age (SGA) stillborn and liveborn fetuses.Methods: This was a multicenter cohort study analyzing data from the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort (2000-2009) and a second cohort of twin pregnancies at St George's University Hospital (SGH) (2011-2016). The STORK cohort was used to compare the performance of the twin charts and non-customized singleton charts of Poon et al. and the SGH cohort was used to validate the twin-specific charts and compare their performance against customized (Gestation Related Optimal Weight (GROW)) and non-customized (Poon) singleton charts. The primary outcome was the prediction of SGA cases that were stillborn and those that were liveborn in twin pregnancies. Estimated fetal weight (EFW) available from the last examination (24 weeks' gestation and onwards) before delivery or demise was used to classify the fetuses as SGA (EFW < 10th centile or < 3rd centile) or appropriate for gestational age. The proportions of predicted SGA stillbirths and SGA live births were calculated using the three different charts.Results: The STORK cohort consisted of 1850 dichorionic (DC) and 300 monochorionic (MC) twin pregnancies. The SGH cohort consisted of 579 DC and 180 MC twin pregnancies. The stillbirth rates in the STORK and SGH cohorts were 1.1% and 1.3%, respectively. In those liveborn in the STORK cohort, using a 10th -centile cut-off to define SGA, the non-customized singleton chart classified a significantly greater proportion as SGA than did the twin chart, regardless of chorionicity (P < 0.001). However, there was no significant difference between the twin and the non-customized singleton charts with regard to the proportion of stillbirth cases that were classified as SGA (P = 0.479). In the SGH cohort, the non-customized singleton chart classified 8.5% of all liveborn fetuses as SGA (EFW < 10th centile) compared with 12.8% using the customized singleton chart and 7.1% using the twin chart (P < 0.001 and P = 0.005, respectively). However, there was no significant difference among the three charts in the proportion of stillbirths classified as SGA, regardless of chorionicity (P = 0.999). Similar results were obtained when the third centile cut-off was used to define SGA.Conclusions: Compared with the STORK chorionicity-specific twin charts, the customized and non-customized singleton charts classified prenatally as SGA more liveborn fetuses. However, the three charts classified as SGA a similar proportion of stillborn cases. Our preliminary results suggest that these twin charts could safely reduce unnecessary medical intervention in twin pregnancies. Further research on the topic is needed before clinical recommendations can be made. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]