Search

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: To compare morbidity, as measured by length of stay in the neonatal intensive care unit (NICU), in twin and singleton gestations classified as small-for-gestational age (SGA) according to estimated fetal weight < 10 th percentile on twin or singleton growth charts., Methods: NICU length of stay was compared in 1150 twins and 29 035 singletons that underwent ultrasound assessment between 35 + 0 and 36 + 6 weeks' gestation. Estimated fetal weight was obtained from measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Gestational age was derived from the first-trimester crown-rump length measurement, using the larger of the two twins. Singletons and twins were compared in terms of NICU admission rate and length of stay according to classification as SGA by the Fetal Medicine Foundation singleton and twin reference distributions., Results: The overall proportions of twins and singletons admitted to NICU were similar (7.3% vs 7.4%), but twins tended to have longer lengths of stay in NICU (≥ 7 days: 2.4% vs 0.8%; relative risk (RR), 3.0 (95% CI, 1.6-4.4)). Using the singleton chart, a higher proportion of twins were classified as SGA compared with singletons (37.6% vs 7.0%). However, the proportion of SGA neonates entering NICU was similar (10.2% for twins and 10.1% for singletons) and the proportion of SGA neonates spending ≥ 7 days in NICU was substantially higher for twins compared with singletons (3.7% vs 1.4%; RR, 2.6 (95% CI, 1.4-4.7))., Conclusions: When singleton charts are used to define SGA in twins and in singletons, there is a greater degree of growth-related neonatal morbidity amongst SGA twins compared with SGA singletons. Consequently, singleton charts do not inappropriately overdiagnose fetal growth restriction in twins and they should be used for monitoring fetal growth in both twins and singletons. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Most of the published literature on selective fetal growth restriction (sFGR) has focused on monochorionic twin pregnancies. The aim of this systematic review was to report on the outcome of dichorionic diamniotic (DCDA) twin pregnancies complicated by sFGR., Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched. The inclusion criteria were DCDA twin pregnancies complicated by sFGR. The outcomes explored were intrauterine death (IUD), neonatal death and perinatal death (PND), survival of at least one and both twins, preterm birth (PTB) (either spontaneous or iatrogenic) prior to 37, 34, 32 and 28 weeks' gestation, pre-eclampsia (PE) or gestational hypertension, neurological, respiratory and infectious morbidity, Apgar score < 7 at 5 min, necrotizing enterocolitis, retinopathy of prematurity and admission to the neonatal intensive care unit (NICU). A composite outcome of neonatal morbidity, defined as the occurrence of respiratory, neurological or infectious morbidity, was also evaluated. Random-effects meta-analysis was used to analyze the data, and results are reported as pooled proportion or odds ratio (OR) with 95% CI., Results: Thirteen studies reporting on 1339 pregnancies with sFGR and 6316 pregnancies without sFGR were included. IUD occurred in 2.6% (95% CI, 1.1-4.7%) of fetuses from DCDA pregnancies with sFGR and 0.6% (95% CI, 0.3-9.7%) of those from DCDA pregnancies without sFGR, while the respective values for PND were 5.2% (95% CI, 3.5-7.3%) and 1.7% (95% CI, 0.1-5.7%). Spontaneous or iatrogenic PTB before 37 weeks complicated 84.1% (95% CI, 55.6-99.2%) of pregnancies with sFGR and 69.1% (95% CI, 45.4-88.4%) of those without sFGR. The respective values for PTB before 34, 32 and 28 weeks were 18.4% (95% CI, 4.4-38.9%), 13.0% (95% CI, 9.5-17.1%) and 1.5% (95% CI, 0.6-2.3%) in pregnancies with sFGR and 10.2% (95% CI, 3.1-20.7%), 7.8% (95% CI, 6.8-9.0%) and 1.8% (95% CI, 1.3-2.4%) in those without sFGR. PE or gestational hypertension complicated 19.9% (95% CI, 12.4-28.6%) of pregnancies with sFGR and 12.8% (95% CI, 10.4-15.4%) of those without sFGR. Composite morbidity occurred in 28.2% (95% CI, 7.8-55.1%) of fetuses from pregnancies with sFGR and 13.9% (95% CI, 6.5-23.5%) of those from pregnancies without sFGR. When stratified according to the sFGR status within a twin pair, composite morbidity occurred in 39.0% (95% CI, 11.1-71.5%) of growth-restricted fetuses and 29.9% (95% CI, 3.5-65.0%) of appropriately grown fetuses (OR, 1.9 (95% CI, 1.7-3.1)), while the respective values for PND were 3.0% (95% CI, 1.8-4.5%) and 1.6% (95% CI, 0.9-2.6%) (OR, 2.1 (95% CI, 1.0-4.1)). On risk analysis, DCDA pregnancies complicated by sFGR had a significantly higher risk of IUD (OR, 5.2 (95% CI, 3.2-8.6)) and composite morbidity or admission to the NICU (OR, 3.2 (95% CI, 1.9-5.6)) compared to those without sFGR, while there was no difference in the risk of PTB before 34 weeks (P = 0.220) or PE/gestational hypertension (P = 0.210)., Conclusions: DCDA twin pregnancies complicated by sFGR are at high risk of perinatal morbidity and mortality. The findings of this systematic review are relevant for counseling and management of complicated DCDA twin pregnancies, in which twin-specific, rather than singleton, outcome data should be used. © 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.)

Objective: To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons., Methods: Gestational-age- and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4391 twin pregnancies with two liveborn fetuses from four European centers, including 3323 dichorionic (DC) and 1068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. EFW was obtained from ultrasound measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton pregnancies. Hierarchical models were fitted to singleton Z-scores with autoregressive terms for serial correlations within the same fetus and between twins from the same pregnancy. Separate models were fitted for DC and MCDA twins., Results: Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestational ages (16 weeks for MCDA and 20 weeks for DC twins). This was followed by a period of catch-up growth until around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50 th percentile was at the 50 th percentile of singleton pregnancies at 23 weeks, the 43 rd percentile at 28 weeks, the 32 nd percentile at 32 weeks and the 22 nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50 th percentile was at the 36 th percentile of singleton pregnancies at 24 weeks, the 29 th percentile at 28 weeks, the 19 th percentile at 32 weeks and the 12 th percentile at 36 weeks., Conclusions: In DC and, to a greater extent, MCDA twin pregnancies, fetal growth is reduced compared with that observed in singleton pregnancies. Furthermore, after 24 weeks, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Birth weight, fetal growth and placental function influence cognitive development. The gradient of these associations is understudied, especially among those with a birth weight considered appropriate-for-gestational age. The aim of this study was to evaluate the associations between birth-weight centile and intellectual development in term/near-term infants across the entire birth-weight spectrum, in order to provide a basis for better understanding of the long-term implications of fetal growth restriction and reduced placental function., Methods: This was a population-based cohort study of 266 440 liveborn singletons from uncomplicated pregnancies, delivered between 36 and 42 weeks of gestation. Perinatal data were obtained from the Dutch Perinatal Registry over the period 2003-2008 and educational data for children aged approximately 12 years were obtained from Statistics Netherlands over the period 2016-2019. Regression analyses were conducted to assess the association of birth-weight centile with school performance. The primary outcomes were mean school performance score, on a scale of 501-550, and proportion of children who reached higher secondary school level., Results: Mean school performance score increased gradually with increasing birth-weight centile, from 533.6 in the 1 st -5 th birth-weight-centile group to 536.8 in the 81 st -85 th birth-weight-centile group. Likewise, the proportion of children at higher secondary school level increased with birth-weight centile, from 43% to 57%. Compared with the 81 st -85 th birth-weight-centile group, mean school performance score and proportion of children at higher secondary school level were significantly lower in all birth-weight-centile groups below the 80 th centile, after adjusting for confounding factors., Conclusions: Birth-weight centile is associated positively with school performance at 12 years of age across the entire birth-weight spectrum, well beyond the conventional and arbitrary cut-offs for suspected fetal growth restriction. This underlines the importance of developing better tools to diagnose fetal growth restriction and reduced placental function, and to identify those at risk for associated short- and long-term consequences. © 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.)

Objectives: To evaluate the prevalence, subtypes and postnatal outcomes of congenital heart defects (CHD) in a cohort of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR), and to compare this population with a cohort of uncomplicated MCDA pregnancies evaluated during the same period., Methods: This was a retrospective analysis of all consecutive MCDA pregnancies referred between 2009 and 2018, including those complicated by sFGR (Group A) and those without complications (Group B). All neonates delivered in our center were screened for CHD before discharge. Discharge letters for all those delivered elsewhere were retrieved. Pregnancies with complications other than sFGR and those without perinatal follow-up were excluded. Pregnancies in Group A were divided into three types according to the Gratacós system of sFGR classification., Results: A total of 870 MCDA twin pregnancies were included: 296 in Group A and 574 in Group B. In Group A, the prevalence of CHD was 3.7% (22/592 twins), with no significant difference in CHD frequency between the three types of sFGR (Type I, 3.7%; Type II, 3.2%; Type III, 4.2%; P = 0.55). Of four Type-III sFGR pregnancies with CHD, one had pulmonary stenosis (PS) in the larger twin and isolated coarctation of the aorta in the smaller cotwin, and three had PS in the larger twin only. No Type-III sFGR pregnancies in which only the smaller twin was affected by CHD were observed. Of 11 CHD cases in the larger twin, 10 (91%) were right ventricular outflow tract abnormalities (RVOTA), and one (9%) was a ventricular septal defect. In the smaller twins, 11 cases of CHD were observed, covering a broad spectrum of cardiac abnormalities. In Group B, the CHD prevalence was 1.1% (13/1148 twins), which was similar to that in the general population, according to the EUROCAT registry for the same period and geographical area of the study (0.96%; P = 0.579). The CHD prevalence was significantly higher in Group A compared with Group B (3.7% vs 1.1%; P = 0.0002; odds ratio, 3.57 (95% CI, 1.78-7.22)). In all pregnancies with CHD in the study population, the anomaly was discordant., Conclusions: In MCDA twin pregnancy, sFGR was associated with a three-fold higher prevalence of CHD. Women with such pregnancies should be referred to a tertiary care hospital for pre- and postnatal cardiac evaluation, treatment and long-term follow-up. In larger twins, the only major CHD observed was RVOTA, while a broad spectrum of CHD was noted in smaller twins. The higher risk of CHD in MCDA pregnancies appears to be due to the typical complications of the monochorionic pregnancy, rather than to the monochorionic nature of the pregnancy itself. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

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 10 th 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., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry., Methods: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection., Results: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM., Conclusions: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Antenatal detection of small-for-gestational age (SGA) can reduce significantly the risk of stillbirth. The Growth Assessment Protocol (GAP) was developed to address the problem that most SGA fetuses are missed antenatally. We set out to analyze the effect that the GAP program has had on stillbirth rates in England., Methods: We analyzed data from 2008 (the year before roll-out of the GAP program) to 2017 (latest available Office for National Statistics (ONS) unit-based data). The program consists of five elements: training, evidence-based guidelines for risk assessment and surveillance of fetal growth, customized charts, recording of process and outcome indicators, and audit of missed SGA cases. All maternity units in England were categorized into one of three groups according to their GAP status in 2017: (1) not in the GAP program; (2) GAP implemented partially (incomplete adoption of protocol, no monitoring and audit); and (3) GAP implemented completely. A subset of the complete-implementation group comprised the 20 units with the highest SGA detection rates. Unit-level live-birth and stillbirth data were obtained from the ONS for each of these groups., Results: Stillbirth rates declined across all groups from 2008 to 2017, and significantly more in units in which GAP was implemented completely than in the non-GAP units (P < 0.05). The steepest decline in stillbirth rate was observed in the 20 units with the highest SGA detection rates, which had a 24% lower stillbirth rate compared with the units not using GAP (P < 0.01) in 2017. This difference remained significant after mixed-effects logistic regression analysis of potential confounding, including social deprivation (odds ratio, 0.76 (95% CI, 0.64-0.90)). Assessment of the nine Bradford Hill causality criteria and associated characteristics suggested that the association between implementation of the GAP program and reduction in stillbirth rate was causal., Conclusions: There has been an overall reduction in stillbirth rates in England that is likely to be a result of increased awareness of the importance of antenatal detection of SGA as a key risk factor for stillbirth. The decline in stillbirth rates was significantly greater in maternity units that had fully implemented the GAP program, and was most pronounced in the units with the highest antenatal SGA detection rates. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

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., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To assess whether prenatal identification of small-for-gestational age (SGA) was associated with lower rates of the primary composite outcome of stillbirth, death in the delivery room or neonatal complications, and secondary outcomes of the composite outcome according to gestational age at delivery, stillbirth and low 5-min Apgar score., Methods: This historical cohort study included women who had a singleton delivery (≥ 32 weeks) between 1994 and 2011 at one of 247 French maternity units. We excluded pregnancies terminated medically, infants with malformations or with missing data on estimated fetal weight or birth weight, and women with missing delivery data. Among the 24 946 infants born SGA (< 5 th percentile), we compared those who had been identified as such prenatally (n = 5093; 20%), with those who had not (n = 19 853; 80%). The main outcome was a composite variable defined as stillbirth or death in the delivery room, or transfer to a neonatal department either immediately or during the neonatal stay in the obstetrics ward. Secondary outcomes were the composite outcome according to gestational age at delivery (32 to < 35 weeks; 35 to < 37 weeks, 37 to < 40 weeks, or ≥ 40 weeks), stillbirth and low 5-min Apgar score (≤ 4 and < 7)., Results: The mean ± SD birth weight was 2449.1 ± 368.3 g. The rate of the main composite outcome was higher in the group identified prenatally as SGA compared with non-identified SGA fetuses (39.5% vs 13.5%; adjusted relative risk (aRR), 1.29; 95% CI, 1.21-1.38). This association was not observed in the subgroups delivered before 37 weeks. The stillbirth rate was lower in fetuses with prenatal suspicion of SGA (aRR, 0.47; 95% CI, 0.27-0.79), while the 5-min Apgar score did not differ between the two groups. The a-posteriori study power with α = 0.05 was 99%., Conclusion: Prenatal identification of SGA was not associated with lower fetal or neonatal morbidity overall, although it was associated with a lower rate of stillbirth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

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 < 10 th 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., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension)., Methods: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10 th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors., Results: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters., Conclusion: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Direct chromosome preparations of chorionic villus samples (CVS) and cell-free DNA (cfDNA) testing both involve analysis of the trophoblastic cell lineage. The aim of this study was to compare the spectrum of rare autosomal trisomies (RATs) detected by these two approaches and assess the available information on their clinical significance., Methods: Data from 10 reports on genome-wide cfDNA testing were pooled to determine which chromosomes were most frequently involved in RAT-positive cases, and pregnancy outcome information was reviewed. CVS information was obtained from an updated database of 76 102 consecutive CVS analyses performed over a period of 18 years at TOMA laboratory, in which trophoblastic and mesenchymal layers were analyzed and amniotic fluid cell analysis was recommended for RAT-positive cases. Chromosomes involved and presence of confined placental mosaicism, true fetal mosaicism and uniparental disomy (UPD) for imprinted chromosomes were assessed. Also evaluated were the frequency and types of RATs in products of conception., Results: RATs were present in 634 of 196 662 (0.32%) cfDNA samples and 237 of 57 539 (0.41%) CVS trophoblast samples (P < 0.01). The frequency of RATs varied over 8-fold between the cfDNA reports. Confirmation of abnormality through amniocentesis was more likely when RATs were ascertained through cfDNA (14 of 151; 9.3%) than through CVS trophoblasts (seven of 237; 3.0%) (P < 0.01). In cfDNA-ascertained cases, trisomies 15, 16 and 22, which are associated with fetal loss, were identified proportionately more often. Of 151 cases with RAT identified by cfDNA and outcome information available, 41.1% resulted in normal live birth; 27.2% in fetal loss; 7.3% had phenotypic abnormality detected through ultrasound or other follow-up evaluation; 2.0% had a clinically significant UPD; and 14.6% had fetal growth restriction or low birth weight. All autosomes were involved in trisomies in products of conception; the most common RATs detected were trisomies 16, 22 and 15 with a frequency of > 9% each., Conclusions: Although there are strong parallels between RATs ascertained through cfDNA analysis and direct chromosome preparation of CVS, caution is needed in applying conclusions from CVS analysis to cfDNA testing, and vice versa. RATs identified through genome-wide cfDNA tests have uncertain risks for fetal loss, growth restriction or fetal abnormality. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Maternal hemodynamics in pregnancy is associated with fetal growth and birth weight, which in turn are associated with offspring cardiovascular disease later in life. The aim of this study was to quantify the extent to which birth weight is associated with cardiac structure and function in adolescence., Methods: A subset of offspring (n = 1964; 55% female) of the Avon Longitudinal Study of Parents and Children were examined with echocardiography at a mean age of 17.7 (SD, 0.3) years. The associations of birth-weight Z-score for sex and gestational age with cardiac structure (assessed by relative wall thickness, left ventricular mass index (LVMI) and left atrial diameter index), systolic function (assessed by ejection fraction and left ventricular wall velocity) and diastolic function (assessed by early/late mitral inflow velocity (E/A) and early mitral inflow velocity/mitral annular early diastolic velocity (E/e')) were evaluated. Linear regression models were adjusted for several potential confounders, including maternal prepregnancy body mass index, age, level of education and smoking during pregnancy., Results: Higher birth-weight Z-score was associated with lower E/A (mean difference, -0.024; 95% CI, -0.043 to -0.005) and E/e' (mean difference, -0.05; 95% CI, -0.10 to -0.001) and higher LVMI (mean difference, 0.38 g/m 2.7 ; 95% CI, 0.09 to 0.67). There was no or inconsistent evidence of associations of birth-weight Z-score with relative wall thickness, left atrial diameter and measurements of systolic function. Further analyses suggested that the association between birth-weight Z-score and LVMI was driven mainly by an association observed in participants born small-for-gestational age and it did not persist when risk factors in adolescence were accounted for., Conclusions: Higher birth weight adjusted for sex and gestational age was associated with differences in measures of diastolic function in adolescence, but the observed associations were small. It remains to be determined the extent to which these associations translate into increased susceptibility to cardiovascular disease later in life. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension., Methods: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21 st )., Results: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3 rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3 rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3 rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3 rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3 rd centile according to INTERGROWTH-21 st charts., Conclusions: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Redistribution of cardiac output (CO) is responsible for the brain-sparing effect seen during periods of fetal stress. Our aim was to investigate prospectively the correlation between fetoplacental Doppler indices and measurements of cardiac function in uncomplicated term singleton pregnancy., Methods: This was a prospective observational study of normotensive women with appropriately grown, non-anomalous singleton pregnancy. Participants underwent fortnightly ultrasound examinations from 36 weeks' gestation until delivery, and intrapartum and neonatal outcomes were recorded. The correlation between fetoplacental Doppler indices and various measurements of cardiac function was evaluated., Results: The study cohort comprised 273 singleton pregnancies. The cerebroplacental ratio (CPR) was correlated positively with left ventricular CO (LVCO) (P < 0.001, rho = 0.29), left-to-right ventricular CO ratio (LVCO/RVCO; P < 0.001, rho = 0.41), global left ventricular strain (P < 0.01, rho = 0.17) and global right ventricular strain (P < 0.001, rho = 0.22). The CPR was correlated inversely with the left ventricular myocardial performance index (P < 0.01, rho = -0.18) and the RVCO (P < 0.001, rho = -0.28). The LVCO and global left ventricular strain were correlated positively with umbilical venous flow (P = 0.04, rho = 0.18 and P < 0.001, rho = 0.25, respectively). There was minimal or no correlation between either the mean uterine artery pulsatility index (PI) or umbilical artery PI with any cardiac indices., Conclusion: The fetal CPR, middle cerebral artery PI and umbilical venous flow are correlated positively with LVCO, LVCO/RVCO and global left ventricular strain in low-risk term pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

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 < 10 th centile or < 3 rd 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 10 th -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 < 10 th 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., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Several studies have investigated the correlation between endometriosis and adverse pregnancy and perinatal outcomes. However, the role of adenomyosis as a risk factor for adverse perinatal outcome in women with endometriosis has yet to be established. The aim of this study was to explore if fetal and maternal outcomes, in particular the incidence of a small-for-gestational-age (SGA) infant, are different in pregnant women with endometriosis only from in those with the concomitant presence of diffuse or focal adenomyosis., Methods: This was a retrospective analysis of data collected prospectively during a 3-year period. We included 206 pregnant women with endometriosis: 148 (71.8%) with endometriosis only, 38 (18.4%) with focal adenomyosis and 20 (9.7%) with diffuse adenomyosis. Adenomyosis was diagnosed using ultrasonography and was classified as focal or diffuse. The study included patients who conceived spontaneously or by an assisted reproductive technique. Demographics, ultrasound variables and outcome were compared between women with endometriosis only and those with diffuse and those with focal adenomyosis. Logistic regression analysis was performed to assess the association of variables with SGA at birth in women with diffuse and those with focal adenomyosis., Results: The three groups were similar in demographic characteristics (age, body mass index, mode of conception). Patients with diffuse adenomyosis compared with those with endometriosis only had significantly lower pregnancy-associated plasma protein A (0.61 vs 0.88 multiple of the median, P < 0.001), higher mean uterine artery pulsatility index in the first (2.23 vs 1.67, P < 0.001) and second (1.30 vs 0.94, P < 0.001) trimesters of pregnancy, and higher incidence of SGA (40% vs 10.8%, P < 0.001). No statistically significant differences were found in patients with focal adenomyosis compared with those with endometriosis only. Logistic regression analysis demonstrated that diffuse adenomyosis (odds ratio = 3.744; 95% CI, 1.158-12.099; P = 0.027) was the only independent risk factor for SGA., Conclusions: The presence of diffuse adenomyosis in pregnant women with endometriosis is strongly associated with delivery of a SGA infant. Women with diffuse adenomyosis should be treated as being at high risk of placental dysfunction, and these pregnancies might therefore need closer monitoring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Women who have delivered a small-for-gestational-age (SGA) infant are at an increased risk of developing cardiovascular disease (CVD) in later life. Endothelial dysfunction is a subclinical sign of early CVD. It is unknown whether women who have recently had a pregnancy complicated by SGA, in the absence of other maternal and fetal diseases, have subclinical endothelial dysfunction. Our aim was to assess maternal endothelial function 6 months after a pregnancy complicated by SGA., Methods: This was a case-control study conducted in a tertiary referral hospital in London, UK, over a 15-month period. Flow-mediated dilatation (FMD) of the brachial artery was measured in women 6.9 ± 2.5 months after childbirth. Forty-four women were included in the study, of whom 15 had a SGA neonate (mean ± SD customized birth centile of 1.9 ± 2.3) and 29 delivered an appropriately grown baby (mean ± SD customized birth centile of 47.5 ± 26.3). The primary continuous variable, FMD, was assessed in each group and compared using unpaired t-test., Results: Women who had a SGA neonate had lower postpartum FMD (6.79 ± 0.95%) than did those who had an appropriately grown offspring (10.26 ± 2.44% (95% CI for difference between groups, -5.37 to -1.57); P = 0.0007). There were no differences in postnatal maternal blood pressure, abdominal circumference, weight and glucose, insulin and lipid profiles between the two groups., Conclusions: Women who had a pregnancy affected by SGA, probably due to placental failure in the absence of pre-eclampsia, have evidence of subclinical endothelial dysfunction within 6 months of childbirth. These women may benefit from lifestyle measures focused on the primary prevention of CVD. Further research in larger populations is needed to ascertain if such postpartum maternal endothelial dysfunction is a pregnancy-induced phenomenon or if it is related to the pre-existing maternal phenotype, and whether it persists long term. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population., Methods: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications., Results: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11))., Conclusions: Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome., Methods: The study group comprised a consecutive series of 338 women with an MCDA pregnancy complicated by twin-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) treated with selective laser photocoagulation of communicating vessels (SLPCV) or cord occlusion (CO). Data obtained included cervical length, gestational age at procedure, type and duration of surgery and placental location. The incidence of CMS, the rates of miscarriage and preterm prelabor rupture of membranes (PPROM), gestational age at delivery and neonatal survival were recorded., Results: Of the study population of MCDA pregnancies, 270 (79.9%) had TTTS and 68 (20.1%) had sIUGR. SLPCV was performed in 252 (74.6%) cases and CO in 86 (25.4%). Postoperative CMS was observed in 70 (20.7%) cases. Patients with CMS had higher rates of miscarriage (14.3% vs 7.1%; P = 0.049), PPROM before 32 weeks (43.3% vs 13.7%; P < 0.001) and preterm delivery before 32 weeks (53.3% vs 26.1%; P < 0.001) and a lower rate of neonatal survival of at least one twin (81.7% vs 93.6%; P = 0.003). Multivariate analysis showed that gestational age at surgery was the only independent predictor, with the highest proportion of CMS occurring in cases that underwent surgery before 18 weeks' gestation (odds ratio, 2.941 (95% CI, 1.640-5.275); P < 0.001). There was no influence of cervical length, placental location, duration of surgery or type of surgery on the risk of CMS., Conclusions: CMS complicated one-fifth of all MCDA pregnancies that underwent fetoscopy. It appeared to be more common in those who underwent surgery before 18 weeks' gestation and was associated with poorer outcomes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To define the contribution of maternal variables which influence the measured level of maternal serum placental growth factor (PlGF) in screening for pregnancy complications., Methods: Maternal characteristics and medical history were recorded and serum levels of PlGF were measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 or 35 + 0 to 37 + 6 weeks' gestation. For women delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history important in the prediction of PlGF were determined from a linear mixed-effects multiple regression., Results: Serum levels of PlGF were measured in 38,002 cases in the first trimester, 10,281 in the second trimester and 12,392 in the third trimester. Significant independent contributions to serum PlGF were provided by gestational age, maternal age, weight and racial origin, cigarette smoking, diabetes mellitus, and gestational age at delivery and birth-weight Z-score of the neonate in the previous pregnancy. The machine used to measure serum PlGF was also found to have a significant effect. Allowing for other factors, the effect of maternal age on PlGF changed over the three trimesters, whereas other variables had constant effects over the three trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured serum PlGF and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this complication., Conclusions: A model was fitted to express the measured level of maternal serum PlGF across the three trimesters of pregnancy as MoMs, after adjusting for variables of maternal characteristics and medical history that affect this measurement., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer an increased risk of neonatal morbidity in late-onset small-for-gestational-age (SGA) fetuses with normal umbilical artery (UA) Doppler indices., Methods: A cohort of 126 SGA singleton fetuses with normal UA Doppler indices that were delivered after 34 weeks' gestation was studied. For each case, the placenta was evaluated histologically for signs of PUP using a hierarchical and standardized classification system. Neonatal morbidity was assessed according to the score calculated from the morbidity assessment index for newborns (MAIN), a validated outcome scale. The independent association between PUP and neonatal morbidity was evaluated using multivariable median regression analysis., Results: In 84 (66.7%) placentae, 97 placental histological findings that qualified as signs of PUP were observed. These PUP cases had a significantly higher incidence of emergency Cesarean section for non-reassuring fetal status (44.1% vs 21.4%, respectively; P = 0.013) and neonatal metabolic acidosis at birth (33.3% vs 14.3%, respectively; P = 0.023), than did those without PUP. The median MAIN score differed significantly between those with PUP and those without (89 vs 0, respectively; P = 0.025). This difference remained significant after adjustment for potential confounders. The proportion of cases with scores indicative of mild to severe morbidity was also significantly higher in the PUP group (31% vs 14.3%, respectively; P = 0.043)., Conclusion: In late-onset SGA fetuses with normal UA Doppler indices, signs of PUP imply a higher neonatal morbidity. These findings allow the phenotypic profiling of fetal growth restriction among the general population of late-onset SGA., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan., Methods: We searched MEDLINE (1948-2012), EMBASE (1980-2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI., Results: We identified three cohort studies and four case-control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case-control studies. Compared to fetuses with a three-vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97-2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9-4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, -154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy., Conclusion: In view of the non-significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To determine the pathological basis and clinical associations of excessively thick placentae observed at second-trimester ultrasound examination., Methods: In a retrospective cohort of 19 singleton high-risk second-trimester pregnancies noted to have a placental length-to-maximum thickness ratio ≤ 2.0, maximum sonographic placental thickness was correlated with clinical outcome, maximum placental thickness after delivery and placental pathological findings. Results were compared with those of an intermediate group of 21 high-risk pregnancies with normal placental dimensions and a control group of 18 low-risk pregnancies also with normal placental dimensions. Increased maximum placental thickness (> 28 mm) and abnormal placental deflation following delivery (pathology - sonography difference in maximum placental thickness < -2 mm) were defined by the upper and lower quartile values, respectively, in the control group., Results: The study group exhibited significantly more adverse outcomes and gross pathological placental features compared with both intermediate and control groups. Despite increased sonographic maximum placental thickness in the study group (median, 55 (range, 40-75) mm compared with both the intermediate group (median, 27 (range, 22-41) mm, P < 0.0001) and the control group (median 26 (range, 23-36) mm, P < 0.0001)), all three groups had similar maximal placental thickness following delivery (study group: median, 24 (range, 10-50) mm vs intermediate group: median, 27 (range, 15-40) mm, P = 0.82 and vs control group: median, 28.5 (range, 18-44), P = 0.42). Pathology-sonography difference in maximum placental thickness in the study group (median, -30 (range, -42 to 0) mm) was significantly greater than that in either the intermediate (median, -2 (range, -11 to 9) mm, P < 0.0001) or the control (median, 1.5 (range, -10 to 18) mm, P < 0.0001) group and was significantly associated with abnormal development of the gas-exchanging placental villi (distal villous hypoplasia) (P = 0.0001)., Conclusions: Increased second-trimester sonographic maximum placental thickness represents a pathological finding associated with severe adverse perinatal outcome. This observation is due to overinflation of the intervillous space by maternal blood rather than to adaptive formation of functional placental tissue., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Our purpose was to evaluate the antenatal incidence of single umbilical artery (SUA) in twin pregnancies according to chorionicity and to assess its relationship with outcome., Methods: Consecutive twin pregnancies undergoing ultrasound evaluation at our institutions were included. A targeted sonographic evaluation of the umbilical cord and vessels was performed in all cases. Chorionicity was determined according to standard ultrasound criteria., Results: A total of 174 twin pregnancies, 100 dichorionic (DC) and 74 monochorionic (MC), were included in the study. An SUA was identified in 17 (9.8%) pregnancies, and in 18 (5.2%) fetuses. No difference was found in the incidence of SUA in DC and MC twins. Among affected pregnancies, all but one DC twin pregnancy were discordant for SUA. Structural and/or chromosomal abnormalities were present in 27.8% of fetuses with SUA. The prevalence of small-for-gestational-age fetuses and of discordant birth weight (> 20% discordance) was higher in the SUA group than in the rest of the population, although these differences were not statistically significant. Twin pairs discordant for SUA had significantly higher weight discordance than those with normal umbilical cords. The sonographic cross-sectional area of the SUA did not appear to show the typical adaptive dilatation usually seen in singleton pregnancies with SUA., Conclusions: The incidence of SUA in twins is higher than in singletons, with no difference between MC and DC twins. Intrapair discordance for SUA in identical twins provides evidence against an exclusively genetic origin of this anomaly. The apparent failure of compensatory dilatation of the umbilical artery in twins with SUA may explain in part the higher risk for fetal growth restriction in these cases., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: To examine early fetal growth, pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) in relation to the risk of delivering a small-for-gestational age (SGA) infant., Methods: Included in the study were 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital, Denmark, between January 2005 and December 2007. Maternal serum levels of PAPP-A and free β-hCG were measured between gestational weeks 8 and 13. Two ultrasound examinations were performed, the first at 11-13 weeks and the second at 18-22 weeks, from which gestational age was estimated based on crown-rump length and biparietal diameter, respectively. Early fetal growth was expressed as an index: the ratio between the estimated number of days from the first to the second scan and the actual calendar time elapsed in days. SGA was defined as birth weight < 5(th) centile for gestational age, and the risk of SGA was evaluated according to different cut-offs of the early fetal growth index and the serum markers., Results: PAPP-A < 0.4 MoM combined with an early fetal growth index < 10(th) centile resulted in an increased risk of SGA (odds ratio (OR), 5.8; 95% CI, 2.7-12.7). Low PAPP-A, low free β-hCG and slow early fetal growth were statistically, independently associated with SGA, and the association between free β-hCG < 0.3 MoM and SGA was as strong as that between PAPP-A < 0.3 MoM and SGA (OR, 3.1 and 3.0, respectively)., Conclusion: The combination of slow early fetal growth and low PAPP-A resulted in a nearly six-fold increased risk of delivery of an SGA infant. These findings might improve our chances of early identification of fetuses at increased risk of growth restriction., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: The aim of this study was to identify predictors of twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD)., Methods: Monochorionic twins with mAFD (n = 45; gestational age, 15-29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52)., Results: Cardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of ≥ 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of ≥ 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS., Conclusion: The outcome of MCDA twins with mAFD remains unpredictable, yet high-risk and low-risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age.

Objectives: To create a fetal size nomogram for use in sub-Saharan Africa and compare the derived centiles with reference intervals from developed countries., Methods: Fetal biometric measurements were obtained at entry to antenatal care (11-22 weeks' gestation) and thereafter at 4-week intervals from pregnant women enrolled in a longitudinal ultrasound study in Kinshasa, Democratic Republic of Congo. The study population comprised 144 singleton gestations with ultrasound-derived gestational age within 14 days of the menstrual estimate. A total of 755 monthly ultrasound scans were included with a mean +/- SD of 5 +/- 1 (range, 2-8) scans per woman. Estimated fetal weight (EFW) was calculated at each ultrasound examination using the Hadlock algorithm. A general mixed-effects linear regression model that incorporated random effects for both the intercept and slope was fitted to log-transformed EFW to account for both mean growth and within-fetus variability in growth. Reference centiles (5(th), 10(th), 50(th), 90(th) and 95(th) centiles) were derived from this model., Results: Nomograms derived from developed populations consistently overestimated the 50(th) centile EFW value for Congolese fetuses by roughly 5-12%. Differences observed in the 10(th) and 90(th) centiles were inconsistent between nomograms, but generally followed a pattern of overestimation that decreased with advancing gestational age., Conclusions: In low-resource settings, endemic malaria and maternal nutritional factors, including low prepregnancy weight and pregnancy weight gain, probably lead to lower fetal weight and utilization of nomograms derived from developed populations is not appropriate. This customized nomogram could provide more applicable reference intervals for diagnosis of intrauterine growth restriction in sub-Saharan African populations.

Objective: To assess the role of maternal demographic characteristics, uterine artery Doppler velocimetry, maternal serum pregnancy-associated plasma protein-A (PAPP-A) and their combination in screening for pre-eclampsia and small-for-gestational age (SGA) fetuses at 11-14 weeks., Methods: This was a prospective study of 878 consecutive women presenting for a routine prenatal ultrasound examination at 11-14 weeks. Pulsed wave Doppler was then used to obtain uterine artery flow velocity waveforms and the mean pulsatility index (PI) of the uterine arteries was calculated. Maternal serum samples for PAPP-A were assayed. Along with maternal history, these measurements were compared in their ability to predict adverse outcome, defined as pre-eclampsia and/or SGA and/or placental abruption., Results: Mean uterine artery PI > or = 95(th) centile and PAPP-A < or = 10(th) centile each predicted 23% of the women that developed pre-eclampsia and 43% of cases of placental abruption. For SGA < or = 5(th) centile, mean uterine artery PI > or = 95(th) centile predicted 23% of cases and PAPP-A < or = 10(th) centile predicted 34%. Independent predictors for subsequent development of pre-eclampsia were increased mean uterine artery PI > or = 95(th) centile (OR, 2.76; 95% CI, 1.11-6.81) and maternal history of pre-eclampsia/hypertension (OR, 50.54; 95% CI, 10.52-242.73). The predicting factors for SGA < or = 5(th) centile were increased mean uterine artery PI > or = 95(th) centile (OR, 2.0; 95% CI, 1.07-3.74) and low PAPP-A (OR, 0.43; 95% CI, 0.20-0.93). Increased uterine artery PI was the only independent factor in the prediction of placental abruption (OR, 8.49; 95% CI, 2.78-25.94). The combination of uterine artery PI and maternal history of pre-eclampsia/hypertension was better than was using uterine artery Doppler alone in predicting pre-eclampsia. Similarly, for the prediction of SGA < or = 5(th) centile, combining uterine artery Doppler and maternal serum PAPP-A was better than was uterine artery Doppler alone. In both cases, the difference approached statistical significance., Conclusions: The combination of maternal history with abnormal uterine artery Doppler and low PAPP-A level at 11-14 weeks achieves better results than does either test alone in the prediction of pre-eclampsia and SGA., (Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: The fetal abdominal circumference is the most sensitive ultrasound biometric measurement for predicting intrauterine growth restriction, which is associated with an increased risk of intrapartum fetal distress. We sought to evaluate and compare whether a third-trimester ultrasound measurement of abdominal circumference made within 1 week prior to delivery better predicts operative delivery for fetal distress when compared with the growth velocity of the abdominal circumference in the third trimester., Methods: Retrospective analysis was carried out of prospectively collected ultrasound data on 117 patients with singleton gestations who had had at least two ultrasound assessments performed less than 6 weeks apart in the third trimester, with the last ultrasound performed within 1 week prior to delivery. The abdominal circumference value of the last ultrasound prior to delivery was placed into one of three categories: < or = 5% centile, > 5 to < or = 10% centile and > 10% centile for gestational age. The growth velocity of the abdominal circumference per week was placed into one of three categories: < or = 5 mm/week, 6-10 mm/week and > or = 11 mm/week. The chi-squared test was used to compare differences between the incidence of fetal distress between the groups., Results: The incidences of Cesarean section for fetal distress in relation to a single measurement of the abdominal circumference were: < or = 5% centile, 8/23 (35%); > 5 to < or = 10% centile, 3/12 (25%); > 10% centile, 8/81 (10%) ( P < 0.05). The incidences of Cesarean section for fetal distress with the three abdominal circumference growth velocities were: < or = 5 mm/week, 9/55 (16%); 6-10 mm/week, 4/11 (36%); > or = 11 mm/week, 8/51 (16%) ( P = 0.9401)., Conclusion: A single measure of the fetal abdominal circumference made within 1 week prior to delivery is superior to an assessment of growth rate of the fetal abdomen in the third trimester in discriminating patients who require Cesarean section for fetal distress.

Objective: Abnormal uterine artery Doppler waveforms in the second trimester of pregnancy can predict adverse outcome. The presence of a diastolic notch is a better predictor than measurement of impedance indices. A notch has generally been assessed subjectively, which has raised questions as to the reproducibility of the method. The aim of this study was to compare subjective and objective assessments of 50 abnormal waveforms., Design: This was a retrospective study of 50 abnormal uterine artery waveforms collected during a previous screening study. Subjective and objective assessments were compared and related to adverse outcomes. Five impedance indices incorporating a measurement of the diastolic notch were compared. Three indices predictive of adverse outcome were compared to subjective assessment., Results: There was good agreement between experienced operators in their subjective assessment of uterine artery waveforms. Adverse outcome was predicted by only moderately or severely abnormal waveforms. Three impedance indices predictive of adverse outcome were the pulsatility index (PI), A/C and (D - C)/B (where A is the peak systolic, D is the maximum diastolic and B is the end-diastolic frequency, and C is the nadir of the notch). The cut-off values combining the highest sensitivity for the lowest false-positive rate were 1.5 for PI, 3.0 for A/C and 0.15 for (D - C)/B. A PI of 1.5 had the highest sensitivity (100%) and positive predictive value (55%) for adverse outcome in this preselected group. These three indices were compared to subjective assessment using the kappa index and the (D - C)/B ratio had the closest agreement, although all three indices showed at least moderate agreement. The cut-off values of 1.5, 3.0 and 0.15 for PI, A/C and (D - C)/B, respectively appear to differentiate between mildly abnormal waveforms and moderately/severely abnormal waveforms., Conclusion: Objective assessment of uterine artery waveforms using cut-off values of PI, A/C and (D - C)/B provides an estimation similar to that provided by subjective assessment by an experienced operator. These ratios will now need to be used prospectively in an unselected population to compare their screening properties.

The objective of this paper was to determine whether first- and second-trimester uterine artery Doppler velocimetry are associated with pregnancy complications in women of advanced maternal age. A prospective cohort study of 352 women aged 35 years and older was studied. The pulsatility index (PI) values at 12-13 weeks of gestation were significantly associated with development of hypertensive disorders, a small-for-gestational-age infant and gestational diabetes, with a relative risk exceeding 4, 2 and 8, respectively for women with PI values in the highest quartile (> 1.67) of the PI distribution when compared with the lowest quartile of the PI distribution (< 1.24). At 23-27 weeks' gestation, uterine artery PI values were found to be associated with preterm delivery with a gestational age-adjusted risk of 10.6 for women with PI values in the highest quartile of PI (> 1.24) when compared with PI values in the lowest quartile of the PI distribution (< 1.09). No associations existed between uterine artery PI, antepartum hemorrhage and Cesarean section rate. The risk estimates for any of the outcome parameters were not affected by maternal age. Results indicate that hemodynamic changes detectable in the uterine artery as early as the first trimester of pregnancy are associated with an increased risk of hypertensive disorders, a small-for-gestational-age infant and gestational diabetes. A similar association exists in the late second trimester of pregnancy, with an increased risk of preterm delivery.

The objectives of this study were to identify, by means of two third-trimester scans, fetuses with ultrasound evidence of inadequate growth but who were born with birth weights above the 10th centile for gestational age; and to determine if these infants constitute a high-risk group by comparing the incidence of obstetric intervention, of intrapartum complications and of neonatal morbidity between this group and the group of infants who showed no ultrasound evidence of intrauterine growth restraint. A total of 285 women with singleton pregnancies who were referred for a third-trimester ultrasound examination were included in this prospective study. Fetal weight was estimated by ultrasound twice in the third trimester and at each examination was assigned a centile score. A fall of > 20 centiles was taken as evidence of inadequate growth. The outcomes measured were the incidence of abnormal umbilical artery Doppler, induction of labor, meconiumstaining of the liquor, intrapartum fetal blood sampling, operative vaginal delivery, Cesarean section, Apgar score of < 7 at 5 min and admission to the neonatal intensive care unit. Seventy-five patients showed a drop of > 20 centiles between the first and second scans. The incidence of admission to the neonatal intensive care unit was greater in those infants who had ultrasound evidence of growth restraint. We conclude that infants of normal birth weight with inadequate growth diagnosed on ultrasound are not at increased risk, they have an increased incidence of admission to the neonatal intensive care unit, and they are more commonly found in mothers with diabetes mellitus.