ISUOG Practice Guidelines (updated): performance of 11–14‐week ultrasound scan

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice and high-quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care, because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG ([email protected]). Performing a routine first-trimester ultrasound examination at 11 + 0 to 14 + 0 weeks' gestation is of value for confirming viability and plurality, accurate pregnancy dating, screening for aneuploidies, identification of major structural anomalies and screening for preterm pre-eclampsia. This document aims to provide guidance for healthcare practitioners performing, or planning to perform, pregnancy scans at 11 + 0 to 14 + 0 weeks. Details of the grades of recommendation and levels of evidence used in ISUOG Guidelines are given in Appendix 1. In general, the main goal of a pregnancy ultrasound scan is to provide accurate information which will facilitate delivery of optimized antenatal care, ensuring the best possible outcomes for mother and fetus. In early pregnancy, it is important to confirm viability, establish gestational age accurately, determine the number of fetuses and, in the presence of a multiple pregnancy, assess chorionicity and amnionicity. Towards the end of the first trimester, the scan also offers an opportunity to detect major fetal abnormalities and, in healthcare systems that offer first-trimester aneuploidy screening, to measure the nuchal translucency (NT) thickness. However, many major malformations may develop later in pregnancy or may not be detected even with appropriate equipment and in the most experienced of hands. If an earlier first-trimester ultrasound scan has not been done, it is advisable to offer the first scan when gestational age is estimated to be between 11 + 0 and 14 + 0 weeks' gestation, as this provides an opportunity to achieve the aforementioned aims, i.e. confirm viability, establish gestational age accurately, determine the number of viable fetuses and, if requested, evaluate fetal anatomy and risk of aneuploidy1-18. Before starting the examination, a healthcare provider should counsel the woman/couple regarding the potential benefits and limitations of the first-trimester ultrasound scan (GOOD PRACTICE POINT). Individuals who perform obstetric scans routinely should have specialized training that is appropriate to the practice of diagnostic ultrasound for pregnant women (GOOD PRACTICE POINT). An examination report should be produced as an electronic and/or paper document (see Appendices 2 and 3 for examples). The document should be stored locally and, in accordance with local protocol, made available to the woman and referring healthcare provider (GOOD PRACTICE POINT). There are no indications that the use of B-mode or M-mode prenatal ultrasonography may be harmful during the first trimester, due to their limited acoustic output20, 21. However, scanning time should be limited and the lowest possible power output should be used to obtain diagnostic information according to the ALARA (As Low As Reasonably Achievable) principle (GOOD PRACTICE POINT). Doppler ultrasound is, however, associated with greater energy output and, therefore, there are more potential bioeffects, especially when it is applied to a small region of interest and in the embryonic period before 11 weeks' gestation20, 22, 23. From 11 + 0 to 14 + 0 weeks, spectral Doppler, color flow imaging, power Doppler imaging and other Doppler ultrasound modalities may be used routinely for certain clinical indications, such as screening for aneuploidies and cardiac anomalies. When performing Doppler ultrasound, the displayed thermal index (TI) should be ≤ 1.0 and the exposure time should be kept as short as possible (usually no longer than 5–10 min). Scanning of the maternal uterine arteries (UtA) at any point in the first trimester is unlikely to have any fetal safety implications as long as the embryo/fetus lies outside the Doppler ultrasound beam22. These Guidelines represent an international benchmark for the first-trimester ultrasound scan, but consideration must be given to local circumstances, protocols and medical practice. If the examination cannot be completed in accordance with these Guidelines, it is advisable to document the reasons for this. In most circumstances, it will be appropriate to repeat the scan, or to refer the case to another healthcare practitioner. This should be done as soon as possible, to minimize unnecessary patient anxiety and any associated delay in achieving the desired goals of the initial examination (GOOD PRACTICE POINT). Determination of chorionicity and amnionicity is important for care, testing and management of multifetal pregnancies. Chorionicity should be determined in early pregnancy, when characterization is most reliable24, 25. Once this is accomplished, further antenatal care, including the timing and frequency of ultrasound examinations, should be planned according to the available health resources and ISUOG or local guidelines26 (GOOD PRACTICE POINT). In early pregnancy, viability is defined by identification of a fetal heartbeat, which is achieved most easily using ultrasound. Fetal cardiac activity can be identified with 2D B-mode ultrasound and the heartbeat can be heard using spectral Doppler. The heart rate, which should be recorded, can be measured using either M-mode or spectral Doppler and is best assessed over a number of cycles (GOOD PRACTICE POINT). Cardiac activity is typically visible from 5–6 weeks' gestation. Heart rate increases with gestational age up to 10 weeks' gestation (mean, 171 bpm) and then decreases through to 14 + 0 weeks' gestation (mean, 156 bpm)27. Fetal tachy- or bradycardia may be indicative of aneuploidy or associated with a structural cardiac abnormality28, 29. If the fetal heart rate lies outside the normal range, it should be reassessed later in the examination. Once viability has been demonstrated, it is important to confirm the intrauterine nature of the pregnancy. An intrauterine gestational sac should be bounded completely by myometrium. This is best assessed by performing a sweep covering the entire uterus (GOOD PRACTICE POINT). The integrity of the uterus may be breached when a pregnancy is located in a Cesarean section scar (see section on ‘Assessment of risk of obstetric complications’) or associated with a rudimentary uterine horn. There are specific charts for assessing first-trimester fetal biometry38. Systematic measurement of cephalic, abdominal and femoral biometry enables documentation of the presence of essential anatomical landmarks, and abnormalities in measurements can reveal early expression of serious pathologies. However, the cut-off values to be used and the follow-up procedures must be decided in accordance with local protocols, in order to avoid an excessive number of false-positive findings or follow-up examinations. Crown–rump length (CRL) should be measured as part of the routine first-trimester scan, either transabdominally or transvaginally (Figure 1a). This measurement should be performed, following standard criteria, with the fetus oriented horizontally on the screen so that the measurement line between crown and rump is at about 90° to the ultrasound beam. The fetus should be in a neutral position (i.e. neither flexed nor hyperextended). The image should be magnified to fill most of the width of the ultrasound screen. Calipers should be placed on the end points of the crown and the rump, which need to be visualized clearly30, 31. The measurement of CRL should be used to estimate gestational age in all cases except in pregnancies conceived by in-vitro fertilization32, 33. When multiple CRL measurements have been taken, gestational age should be assessed based on the best-quality CRL measurement between 45 and 84 mm. A number of different charts have been published and there are small but significant variations in reported measurements for gestational age34. Although older charts are still used widely, it is recommended to use recent, international, prescriptive charts35, because these take into account improvements in image and machine quality and aim to avoid possible statistical bias36, 37. The CRL (and not the calculated gestational age) should be used as a gestational reference to define where measurements of NT, UtA Doppler pulsatility index (PI) and biochemical markers free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) lie in relation to the normal range. The CRL is reduced in fetuses affected by trisomy 18 and triploidy, and care should be taken not to ‘normalize’ findings by changing dates in fetuses that have obvious structural anomalies. Particular attention should be paid if the CRL is smaller than expected based on an earlier ultrasound measurement. Biparietal diameter (BPD) and head circumference are measured in the largest symmetrical axial view of the fetal head (Figure 1b). Two techniques for measurement of BPD have been described, placing calipers outer-to-inner (leading edge) or outer-to-outer, perpendicular to the midline falx. Measurements should be made in accordance with the methodology used to establish the nomogram employed. BPD measurements adjusted for CRL38 and/or abdominal circumference (AC) or transverse abdominal diameter (TAD) may be useful in early screening for myelomeningocele39-42 and holoprosencephaly43. AC is measured in an axial section of the fetal abdomen at the level in which the stomach is visualized (Figure 1c), at the outer surface of the skin line. It is either measured directly with ellipse calipers or calculated from perpendicular linear measurements, usually the anteroposterior abdominal diameter (APAD) and TAD. To measure APAD, the calipers are placed on the outer borders of the body outline, from the posterior aspect (skin covering the spine) to the anterior abdominal wall. To measure TAD, the calipers are placed on the outer borders of the body outline, across the abdomen at the widest point. AC may be calculated using the formula: AC = π (APAD + TAD)/2 = 1.57 (APAD + TAD). An advantage of performing this measurement is that the image used to record it also shows the stomach in place. Femur length is measured in the long-axis plane of the femur (Figure 1d). The calipers are placed at either end of the ossified diaphysis, which is clearly visible. An advantage of performing this measurement is that it ensures that the sonographer checks the development of the lower limbs which may reveal early the presence of severe skeletal anomalies44. Successful early detection of fetal structural anomalies is also dependent on the standard of equipment available for screening, the skill set of the sonographers and sonologists and the prevalence of the anomalies in the population. Some sonographic features of structural abnormality have been described only relatively recently, and it is not yet clear how these markers perform in population screening. We therefore describe two levels of screening, presenting both a checklist of ‘minimum requirements’ for a basic structural survey at 11 + 0 to 14 + 0 weeks' gestation (Table 1) and a more advanced level of ‘best practice’ for comprehensive detailed examination of the fetus in the first trimester (Table 2). There is currently limited evidence describing the health economic benefit of early identification of fetal structural abnormalities. Axial view of head: Calcification of cranium Contour/shape of cranium (with no bony defects) Two brain halves separated by interhemispheric falx Choroid plexuses almost filling lateral ventricles in their posterior two- thirds (butterfly sign) Sagittal view of head and neck: Confirm whether nuchal translucency thickness < 95th percentile Axial view of heart at level of four-chamber view: Heart inside chest with regular rhythm Axial view: Stomach visible Intact abdominal wall Axial or sagittal view: Bladder visible and not dilated Sagittal view: Crown–rump length and nuchal translucency thickness Axial view: Biparietal diameter Calcification of cranium Contour/shape of cranium (with no bony defects) Two brain halves separated by interhemispheric falx Choroid plexuses almost filling lateral ventricles in their posterior two-thirds (butterfly sign) Thalami Brainstem Cerebral peduncles with aqueduct of Sylvius Intracranial translucency (fourth ventricle) Cisterna magna Forehead Bilateral orbits Nasal bone Maxilla Retronasal triangle Upper lip Mandible Nuchal translucency thickness No jugular cysts in neck Shape of the thoracic wall Lung fields Diaphragmatic continuity Heart activity present with regular heart rhythm Establish situs Position: intrathoracic heart position with cardiac axis to left (30–60°) Size: one-third of thoracic space Four-chamber view with two distinct ventricles on grayscale and color Doppler in diastole Left ventricular outflow tract view on grayscale or color Doppler Three-vessel-and-trachea view on grayscale or color Doppler Absence of tricuspid regurgitation/antegrade ductus venosus A-wave on pulsed-wave Doppler Stomach: normal position in left upper abdomen Bladder: normally filled in pelvis (longitudinal diameter < 7 mm) Abdominal wall: intact with umbilical cord insertion Two umbilical arteries bordering bladder Kidneys: bilateral presence Upper limbs with three segments and free movement Lower limbs with three segments and free movement Size and texture normal, without cystic appearance Location in relation to cervix and to previous uterine Cesarean section scar Cord insertion into placenta Amniotic fluid volume Amniotic membrane and chorion dissociated physiologically The 11 + 0 to 14 + 0-week scan provides an opportunity to assess fetal anatomy and should not be limited to assessment of fetal CRL and NT. Whilst cell-free (cf) DNA provides a highly effective means of screening for common aneuploidies, this test cannot identify structural defects, which may be associated with a more extensive range of rarer chromosomal abnormalities. Identification of a structural abnormality may support an invasive rather than a non-invasive approach to testing for aneuploidy48-50. Several severe structural anomalies can be detected in almost all cases45 and their presence or absence should be assessed as a minimum standard in all patients presenting for an 11 + 0 to 14 + 0-week scan (GOOD PRACTICE POINT). Most structural anomalies occur in pregnancies categorized as being at ‘low risk’ by traditional (history-based) approaches to screening. Effective detection of structural anomalies therefore relies on routine examination of the whole population rather than examination of predefined risk groups only. Demonstration of normal anatomy at 11 + 0 to 14 + 0 weeks provides early reassurance for most pregnant women. Early identification of a major anomaly allows earlier genetic diagnosis and more time for parental counseling and decision-making. Detailed assessment of fetal anatomy at 11 + 0 to 14 + 0 weeks is best achieved using high-resolution transabdominal and transvaginal transducers. Both transabdominal and transvaginal approaches may be required to complete a systematic examination of fetal organs and adequate time needs to be scheduled for this assessment. While a transvaginal examination is not mandatory, it may provide better image resolution for the assessment of fetal anatomy, especially in women with increased body mass index, uterine fibroids and/or retroverted uterus. Within this 3-week time interval, the fetus almost doubles in size (CRL, 45–84 mm). Visualization of many anatomical details by ultrasound is best achieved at around 13 weeks' gestation (GOOD PRACTICE POINT). Several studies have shown that the adoption of a systematic examination including a standardized protocol is associated with a significant increase in the detection rate of anomalies in early gestation46, 47, 51, 52. As sonographers and sonologists gain more experience in screening at 11 + 0 to 14 + 0 weeks, changing from a protocol based on ‘minimum requirements’ to a more extensive ‘best-practice’ systematic review will allow detection of a higher proportion and a wider range of structural anomalies. A systematic approach to detailed assessment of the fetal anatomy at 11 + 0 to 14 + 0 weeks should include the following (Table 2). Overview of fetus, placenta and uterus. An overview of the fetus should be assessed (Figure 2a). The placenta should appear as slightly echogenic, with uniform, homogeneous echotexture, without small or large cysts or lacunae (Figure 2b). The presence or absence of a subchorionic hematoma should be assessed. Prediction of the final placental location in relation to the internal cervical os can be challenging in the first trimester and subject to false-positive reporting of low-lying placenta. However, in a patient with a history of a previous Cesarean section, a careful assessment of the placenta could help in the early detection of an abnormal invasive placenta. This is discussed in the section on ‘Assessment of risk of obstetric complications’. Within the uterus, the presence or absence of fibroids, amniotic bands and synechiae should be evaluated. Amniotic fluid and membranes. A change in amniotic fluid volume is rarely observed in early gestation, so, unlike in the second-trimester scan, this cannot be used as a hint for anomalies. The amniotic membranes are often well visualized as a sac surrounding the fetus and not yet fused with the chorion. When there is a history of bleeding, a blood clot is often identified in the retroamniotic space. In multiple pregnancy, chorionicity and amnionicity should be determined and documented (Figure 2c). Head and brain. Examination of the fetal head and central nervous system is best achieved using a combination of axial and midsagittal planes. The axial plane is used to visualize ossification of the skull and the symmetry of the developing brain structures. Cranial bone ossification should be visible by 11 completed gestational weeks. The cerebral region is dominated by lateral ventricles that appear large and are almost filled in their posterior two-thirds with the slightly asymmetric echogenic choroid plexuses (Figure 2d). The hemispheres appear symmetrical and are separated by the interhemispheric fissure and falx. The brain mantle is very thin and best appreciated anteriorly, lining the large fluid-filled ventricles (Figure 2e). A lower plane within the head shows the two thalami and the posterior fossa region with the cerebral peduncles and the aqueduct of Sylvius, the fourth ventricle and the future cisterna magna as fluid-filled structures (Figure 2f). A midsagittal plane of the head/face can also be used to assess the posterior fossa and visualize the intracranial translucency (fourth ventricle) and brainstem as a screening test for open neural tube defects and cystic posterior fossa malformations (Figure 2g). Fetal face. Visualization of the fetal face is best achieved in the midsagittal plane, which should be complemented with examination in either an axial or a coronal plane. The magnified midsagittal plane of the head and neck enables assessment of several anatomic regions of the face, including the forehead, nasal bone, maxilla, mandible and mouth (Figure 2g). Different facial angles and markers (e.g. maxillary gap, superimposed-line sign) have been proposed to assess the presence of facial clefts in the midsagittal view but these need confirmation in other planes53, 54. In an axial or coronal view an attempt should be made to visualize the eyes with their interorbital distance and the retronasal triangle, demonstrating the maxilla and the mandible (Figure 2h and 2i). The nasal bone is ‘absent’ or hypoplastic in 50–60% of fetuses with trisomy 21 and this can be used as an additional marker to improve efficacy of ultrasound-based screening. Neck. Sonographic assessment and measurement of NT should be part of the screening protocol (Figure 1e), independent of whether it is used for risk assessment for aneuploidy. Increased NT may be a marker for rarer aneuploidies in pregnancy, while cfDNA has been used mostly to screen for a more limited range of common aneuploidies. The standardized method for measurement of NT is reviewed in the aneuploidy section of these Guidelines. Other discrete fluid-filled collections may be seen in the sides of the neck and are associated with dilated jugular lymph sacs and cystic hygroma. NT is increased in up to 40% of fetuses that have a major cardiac abnormality and is associated with other structural and genetic anomalies and an increased risk of intrauterine fetal death55, 56. Thorax and heart. The thoracic cavity with lungs and heart are evaluated in the fetal four-chamber plane (Figure 2j). In this plane, the ribs, lungs, situs and cardiac position in the chest are assessed, with the cardiac axis pointing to the left (the normal axis is at 30–60°)57, 58. The lungs should appear homogeneously echogenic, and there should be no sign of pleural effusion. Diaphragmatic continuity is evaluated in an axial, sagittal/parasagittal or coronal plane, noting normal intra-abdominal position of the stomach and liver. Early assessment of the fetal heart is achieved more reliably by combining grayscale with color Doppler imaging. Color Doppler helps to confirm the presence of two distinct ventricles with separate filling in diastole and to exclude significant atrioventricular valve regurgitation (Figure 2k). Examination of the great vessels through identification of the left ventricular outflow tract and three-vessel-and-trachea view with color Doppler demonstrates the presence, number and size of the great vessels, their anatomic relationship and the direction of blood flow, along with the continuity of the ductal and aortic arches, enabling ruling out of most complex anomalies affecting the great vessels (Figure 2l). Multicenter studies have shown better detection rates of cardiac anomaly when using multiple planes in addition to the use of color Doppler59. Abdominal content. The stomach and bladder are the only echolucent fluid-filled structures in the abdomen and pelvis. The position of the stomach on the left side of the abdomen, together with levocardia, helps confirm normal visceral situs (Figure 2m). The fetal kidneys can often be seen in their expected paraspinal location as bean-shaped, slightly echogenic structures, with typical hypoechoic central renal pelvis (Figure 2r). By 12 weeks' gestation, the fetal bladder should be visible as a median hypoechoic round structure in the lower abdomen, with a longitudinal diameter < 7 mm (Figure 2p and 2q). Abdominal wall. The normal insertion of the umbilical cord should be documented after 12 weeks (Figure 2n). Physiologic midgut herniation is present up to 11 weeks and should be differentiated from omphalocele and gastroschisis. Umbilical cord. The number of cord vessels and the cord insertion at the umbilicus should be noted. Brief evaluation of the paravesical region with color or power Doppler can be helpful in confirming the presence of two umbilical arteries (Figure 2o). Single umbilical artery (SUA) does not constitute an anomaly, but is associated with congenital anomalies and fetal growth restriction. Care should be taken not to cause anxiety to the parents when SUA is detected, if no major anomaly is found at the first-trimester scan. There is, as yet, no consensus regarding the potential impact of SUA on pregnancy outcome. Placental cord insertion can also be assessed reliably at this stage with color Doppler. Spine. The spine should be examined, when possible, in a sagittal view, to assess vertebral alignment and integrity of skin covering (Figure 2s). Vertebral bodies are ossified after 12 weeks' gestation. Particular attention should be paid to the appearance of the spine when any intracranial signs suspicious for open spina bifida are found60. Limbs. Presence of the three segments of both upper and lower limbs and presence and normal orientation of the two hands and feet should be noted at the 11 + 0 to 14 + 0-week ultrasound scan (Figure 2t and 2u). Genitalia. Evaluation of the external genitalia and fetal sex is based upon the orientation of the genital tubercle in the sagittal plane (Figure 2q). Role of three-dimensional (3D) and four-dimensional (4D) ultrasound. 3D and 4D ultrasound are not currently used for routine first-trimester fetal anatomical evaluation. However, in experienced hands, these methods may be helpful in evaluation of abnormalities, especially with multiplanar reconstruction of selected diagnostic planes. There are two tests that are generally used to screen for common aneuploidies: combined first-trimester screening (includes risks derived from maternal history, ultrasound and maternal serum biochemistry); and cfDNA testing (also known as non-invasive prenatal testing (NIPT) or non-invasive prenatal screening (NIPS)). Combined first-trimester screening tests for common trisomies, which comprise approximately 50% of all genetic aberrations identifiable prenatally by array-based genomic assessment. Combined first-trimester screening is also effective to diagnose Turner syndrome. cfDNA testing may be extended to include other aneuploidies, including microdeletions and microduplications. The range of conditions for which testing is carried out is dependent on the test provider. Most clinicians using combined first-trimester screening to calculate risks for the common aneuploidies, i.e. trisomies 21, 18 and 13, use a risk algorithm that is freely available from The Fetal Medicine Foundation61, 62. The basic algorithm combines an a-priori risk based on maternal age, gestational age and maternal history of previous pregnancy with trisomy 21, 18 or 13 with ultrasound measurement of NT thickness and assessment of maternal serum free β-hCG and PAPP-A63, 64. The a-priori risk is altered by multiplying it by a likelihood ratio derived for each of these factors. Likelihood ratios are calculated by comparing frequency distributions for each specific marker in chromosomally normal and abnormal populations. The NT is measured with cross calipers placed on its echogenic margins. Three measurements should be made (on separate images) and the largest is used for risk assessment. The correct, standardized technique for NT measurement has been described by Nicolaides65. As this measurement is used to calculate a likelihood ratio for risk calculation, accurate assessment is essential. This is achieved by restricting performance of NT measurement to trained personnel who agree to undergo a continuous process of quality assurance that compares reported measures to a recognized international standard. Some quality-assurance programs are run nationally; others allow sonographers to participate internationally (www.fetalmedicine.org). First-trimester screening efficacy is improved by combining ultrasound-based NT measurement with assessment of maternal free β-hCG and PAPP-A. Most national guidelines recommend combining these markers when screening for trisomies 21, 18 and 13. These markers show different patterns of up- or down-regulation in the three common trisomies, which enables individualized risk assessment for each of these aneuploidies. Recently, data have demonstrated that low maternal serum concentrations of PlGF at 11 + 0 to 14 + 0 weeks' gestation are associated with common trisomies, suggesting that PlGF can be incorporated within the risk calculation, especially when it has already been measured in screening for preterm pre-eclampsia (see section on ‘Assessment of risk of obstetric complications’). Nasal bone. Several other ultrasound markers for aneuploidy have been described. Delayed ossification of the nasal bone, reported as ‘hypoplastic’ or ‘absence of the’ nasal bone at 11 + 0 to 14 + 0 weeks' gestation, is a powerful marker in screening for trisomy 21. The nasal bone is rarely hypoplastic or absent in euploid fetuses and consequently this dichotomized variable is associated with large positive and negative likelihood ratios66-69. This potentially allows significant improvement in specificity whilst maintaining high sensitivity69. The nasal bone is assessed in the same midsagittal section as NT, with a magnified image that includes the echogenic tip of the nose and the rectangular shape of the palate anteriorly. Posterior to it, and centrally in the brain, the translucent diencephalon and the nuchal membrane can be identified. The nasal bone lies below the echogenic skin line of the face. The nasal bone should normally be more echogenic than the skin at the tip and the bridge of the nose, which lies immediately above the bone itself (Figure 1e)67. If the nasal bone cannot be demonstrated to be more echogenic than the skin above, then it is deemed hypoplastic or absent. Ductus venosus flow (Figure 1f). Fetuses affected by aneuploidy are more likely to have