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Should second trimester ultrasound be routine for all pregnancies?

Michel Makhlouf, MD, PhD, and George Saade, MDn
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555

ART IC LE INFO

AB ST R A CT
Ultrasound use has become ubiquitous in pregnancy. We review the evidence regarding

Keywords: Ultrasound Routine Second trimester Pregnancy

the benets of routine ultrasound use during pregnancy. Routine ultrasound use before 24 weeks improves detection of undiagnosed twins, reduces postdates inductions, and allows detection of fetal anomalies before birth. Wide variations exist in the sensitivity of ultrasound in detecting fetal anomalies. These may be related to equipment, training, and maternal characteristics, such as obesity. Standards have been developed for the performance of routine fetal ultrasonography in the second trimester. The benets of routine rst trimester ultrasound in the diagnosis of structural fetal anomalies or of routine ultrasonography after 24 weeks are not proven. As ultrasound technology improves and obstetrical care changes, new uses of routine ultrasonography may emerge. & 2013 Elsevier Inc. All rights reserved.

1.

Benets of second trimester ultrasound

Ultrasound use has become more frequent during pregnancy. In the developed world, an ultrasound evaluation is performed at some point during gestation for the vast majority of pregnancies. In many countries, ultrasonography has become routine. The most studied benet of routine ultrasonography is that of exams conducted in the second trimester. Whitworth et al.1 conducted a review of 11 randomized and quasi-randomized trials evaluating pregnant women undergoing selective ultrasound versus routine ultrasound at less than 24 weeks. The primary outcomes for the review were the early detection of fetal anomalies, detection of multiple gestation by 24 weeks, rate of postdate induction, and rate of perinatal death. The trials included in the overall systematic review enrolled a total of 37,505 women, with the earliest trial recruiting patients in the 1970s. Early routine ultrasound was associated with increased detection of fetal abnormalities before 24 weeks (two trials, 17,158 pregnancies, 387 fetal abnormalities, 16% detected in the
n

early ultrasound versus 4% in the unscreened group; risk ratio (RR) of 3.46, 95% condence interval (CI) 1.677.14) although the majority of the anomalies were not detected. Similarly, ultrasound was associated with earlier detection of twins or multiple gestation: in the screened group, two of 153 multiple gestations were undetected at 24 weeks compared to 56 of 142 in the control groups (seven trials, 295 multiple gestations; RR 0.07, 95% CI 0.030.17). The screened groups also had lower rates of induction for postdates (eight trials, 25,516 women; RR 0.59, 95% CI 0.420.83) as well as induction for any reason (seven trials, 24,790 women; RR 0.78, 95% CI 0.630.97). The effect on induction for postdates was not substantially different when only studies in which ultrasound was performed after 14 weeks were analyzed (ve trials, 23,434 women; RR 0.49, 95% CI 0.310.77). There was no difference in the perinatal mortality between the two groups overall (10 trials, 35,735 participants; RR 0.89, 95% CI 0.701.12) nor for those pregnancies without known lethal anomalies (eight trials, 34,331 participants; RR 0.96, 95% CI 0.721.27).

Corresponding author. E-mail address: gsaade@utmb.edu (G. Saade).

0146-0005/13/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semperi.2013.06.008

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The authors also compared detection of fetal anomalies and multiple gestations all the way up to delivery. The screened group had higher rates of fetal anomaly detection before birth (two trials, 387 fetal abnormalities; RR 3.19, 95% CI 1.995.11). In the screened group, all multiple gestations were detected before labor, whereas 12/133 multiple gestations remained undetected in the control group (ve trials, 273 multiple gestations; RR 0.12, 95% CI 0.030.54). Neonatal outcomes were similar between the two groups: there was no difference in mean birth weight, rate of low birth weight (o1500 g) or very low birth weight (o2500 g), Apgar scores, or admission to neonatal intensive care. Similarly, in the studies in which the offspring were evaluated in childhood and adolescence, there was no signicant difference in school performance. Finally, with regard to maternal outcomes, there was no difference in the rate of cesarean delivery. Additionally, the number of prenatal visits and hospital admissions was similar between the two groups. The sensitivity of routine ultrasonography in the detection of fetal anomalies was also evaluated in the Eurofetus study.2 The study was conducted from January 1990 to June 1993 in the 61 centers across Europe. In this prospective study, all malformations diagnosed by ultrasound were included. Additionally, malformations detected at birth that were not detected by ultrasound were also reported. The trial only included ultrasound examinations performed as routine. The exams were performed by qualied personnel with level 2type equipment. The detection rate of fetal malformations in the study was 56%. Major anomalies were more frequently detected (73.7%) compared to minor anomalies (45.7%). Urinary system anomalies and central nervous system anomalies had the highest detection rates (88.5% and 88.3% respectively). The detection rate of major cardiac anomalies was 38.8% and that of minor ones was 20.8%. The lowest rates of detection were for minor abnormalities of the musculoskeletal system (18%) and for cleft lip and palate (18%). The study also provided valuable information regarding the falsepositive rates of ultrasound examinations. Of the 3085 diagnoses of malformation made during pregnancy, 2593 (84%) were true positives and 492 (16%) were false positives. Of the false positives, 187 (6%) were realized as false positives and the diagnosis was corrected during the pregnancy. Of the 305 false-positive cases identied after birth, 49 were in fetuses with other correctly identied abnormalities and 256 were false positives in a normal fetus. As part of its prenatal care guidelines published in 2003 and updated in 2008, The National Institute for Health and Clinical Excellence (NICE) evaluated the diagnostic value of routine ultrasound in the second trimester.3 In a systematic review of 17 studies, the sensitivity of detection of fetal anomalies prior to 24 weeks was 24%, with a wide range between studies from 13.5% to 87.5%. Specicity was 99.92% (range 99.4100%). The overall sensitivity and specicity irrespective of gestational age at detection were 35.4% (range 1592.9%) and 99.86% (range 99.4100%), respectively. In the report, however, the overall detection rate for lethal fetal anomalies was 84%. Meta-analysis showed positive likelihood ratio of 541.54 (95% CI 430.860.76) and negative likelihood ratio of 0.56 (95% CI 0.540.58) for diagnosis before 24 weeks,

and positive likelihood ratio of 242.89 (95% CI 218.35270.18) and negative likelihood ratio of 0.65 (95% CI 0.630.66) for overall diagnosis. Based on these ndings, NICE recommended that ultrasound screening for fetal anomalies should be routinely offered and performed between 18 0/7 and 20 6/7 weeks for pregnant women who choose to have screening. This recommendation is separate from recommendations regarding earlier ultrasounds to determine gestational age or screen for aneuploidy, both of which are addressed in a separate articles in this issue. NICE also evaluated the detection rate of routine fetal echocardiography as part of the anatomic assessment. None of the studies identied were randomized. In the identied studies, fetal echocardiography consisted of assessing the four chamber view and outow tracts. Color Doppler ow mapping and venous return evaluation were performed in select studies. The detection rate ranged from 16.7% to 94% for major cardiac anomalies and 3.682.1% for minor anomalies. There were no randomized trials evaluating the usefulness of routine fetal echocardiography. In a cohort study by Bonnet et al.,4 the outcomes of neonates in whom transposition of the great arteries (TGA) was diagnosed prenatally was compared to those of neonates with TGA diagnosed after birth. Metabolic acidosis, multi-organ failure, and preoperative mortality were worse in the group diagnosed postnatally. Postoperative mortality was also increased in the postnatal identication group. These results suggest that earlier identication of TGA is associated with improved outcomes.

2. Factors affecting usefulness of second trimester ultrasound

Maternal factors also play a role in the detection rate of fetal anomalies. In a secondary analysis of the First and Second Trimester Evaluation of Risk (FaSTER) trial, AagaardTillery et al.5 observed a lower rate of detection of cardiac anomalies in women with a BMI 430 compared to those with a BMI o25. Following logistic regression, maternal obesity was associated with a signicantly decreased likelihood of detection of common fetal anomalies. Of note, the exams were genetic sonograms with more detailed imaging than the routine second trimester sonogram. In a retrospective analysis, Dashe et al.6 noted decreased detection of fetal anomalies with increasing maternal BMI. With standard ultrasonography, the detection rate of fetal anomalies was 25% in women with class III obesity as opposed to 66% in women with normal BMI. Gestational age is another factor affecting detection by ultrasound. There is limited information about the diagnostic value of ultrasound in the rst trimester in the detection of fetal structural anomalies. In a prospective study of 6634 women enrolled at o15 weeks gestation, Whitlow et al.7 performed an early anatomical ultrasound survey in combination with a second trimester survey. Twenty percent of the subjects also underwent trans-vaginal examination in early pregnancy. The detection rate for fetal anomalies was 59% with the early ultrasound but increased to 81% when combined with the second trimester ultrasound. In a Swedish

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randomized trial of 39,572 subjects comparing ultrasound exams at 12 weeks versus 18 weeks, the detection rate of major structural anomalies was 38% in the early evaluation group versus 47% in the second trimester group (P 0.06).8 A NICE health technology assessment review suggested that second trimester ultrasound is the most cost-effective way of screening for fetal anomalies.3 Similar recommendations for routine anatomic screening ultrasound have also been endorsed by the Society of Obstetricians and Gynaecologists of Canada (between 18 and 22 weeks) and the American College of Obstetricians and Gynecologists (between 18 and 20 weeks).9,10 The value of routine ultrasound examination after 24 weeks was also evaluated in a systematic review of eight trials enrolling 27,024 subjects.11 The trials differed with respect to ultrasound exams allowed before 24 weeks, but all compared subjects who received routine ultrasound after 24 weeks to those with selective exams. There was no difference between the groups in the rates of additional antenatal testing, induction of labor, or instrumented delivery. The group undergoing routine exams had higher rates of cesarean delivery, although this was not statistically signicant, but had lower rates of post-term delivery. There were no differences in the 5-minute Apgar score, neonatal interventions, or moderate or severe neonatal morbidity.11,12

Institute of Ultrasound Medicine, the American College of Radiology, and the American College of Obstetricians and Gynecologists.9,10,13,14 The detailed ultrasound examination, which is not routine for all patients, includes further assessment of anatomic detail.15 In addition to the components listed in the basic examination, the evaluation of the following structures is performed: lateral, third, and fourth ventricles; cisterna magna measurement; nuchal thickness measurement; examination of the brain parenchyma; upper lip integrity; palate mandible; facial prole; and orbital size and separation. The neck and chest are examined for masses and the presence of pleural effusion, integrity of the diaphragm, and appearance of the lung parenchyma and ribs. The heart is evaluated for echogenicity, position, and axis, and appearance and relationship of the outow tracts. The abdomen and extremities are also evaluated in more detail, including anatomy and position of the hands and feet.

4. Emerging indications for second trimester ultrasound

New indications for routine ultrasonography in pregnancy are emerging. The use of routine ultrasonography to screen for short cervical length in pregnancy has been advocated by some to reduce the rates of preterm delivery. In two randomized trials, progesterone treatment was associated with reduced preterm delivery in low-risk subjects with a short cervical length on ultrasound screening.16,17 However, this approach has not gained universal acceptance: quality assurance, lack of availability of screening, and the potential for patients to receive unnecessary interventions are cited as issues that must be addressed before universal acceptance.18 In summary, ultrasound use has become ubiquitous during pregnancy. Routine second trimester evaluation for fetal number, conrmation of gestational age, and fetal anatomy is associated with improved anomaly detection, better identications of multiple gestation, and reduced induction of labor for postdates. A routine second trimester ultrasound is recommended by a number of organizations. There is wide variation in the detection rate and this may be inuenced by maternal habitus. As ultrasound technology improves and obstetrical care changes, new indications for routine ultrasonography may arise.

3.

Content of the second trimester ultrasound

Several organizations have recommended standardization of the anatomic ultrasound. At a minimum, the examination should include determining fetal number, fetal presentation, and cardiac activity. For multiple gestations, chronicity and number of amniotic sacs should also be reported. Biometric measurements of the biparietal diameter, head circumference, abdominal circumference, and femur length should be obtained. Measurements of the following structures are also routinely obtained in the basic assessment: nuchal fold, cisterna magna, cerebellar diameter, and width of the lateral ventricle. Regarding anatomic evaluation of fetal structures, the following structures should be imaged, along with a designation as normal or description of abnormal ndings as noted: cranium, cerebral ventricles, cavum septi pellucidi, the midline falx, the choroid plexus, cisterna magna, cerebellum, orbits, lips, fetal spine, chest, stomach, bowel, kidneys bladder, abdominal cord insertion, number of vessels in the umbilical cord, and presence of upper and lower extremities including hands and feet. Fetal gender should also be determined. The fetal heart is also evaluated; cardiac position and cardiac axis are determined. Imaging of the four-chamber view is obtained and attempts are made to image and document the relationship of the outow tracts. In addition to anatomic structures, an assessment of amniotic uid and the location of the placenta, especially with respect to the cervical os, are also reported. Imaging of the uterus and maternal adnexa is also obtained and uterine and adnexal pathology, if present, are reported.9 These standards for the basic ultrasound examination have been adopted by the Society of Maternal Fetal Medicine, the American

refere nces

1 Whitworth M, Bricker L, Neilson JP, Dowswell T. Ultrasound for fetal assessment in early pregnancy. Cochrane Database Syst Rev. 2010(4):CD007058. 2 Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study. Am J Obstet Gynecol. 1999;181(2):446454. 3 National Collaborating Centre for Women's and Children's Health. In: Antenatal Care: Routine Care for the Healthy Pregnant Woman. London: RCOG Press; 2008. 4 Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation. 1999;99(7):916918.

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5 Aagaard-Tillery KM, Flint Porter T, Malone FD, et al. Inuence of maternal BMI on genetic sonography in the FaSTER trial. Prenat Diagn. 2010;30(1):1422. 6 Dashe JS, McIntire DD, Twickler DM. Effect of maternal obesity on the ultrasound detection of anomalous fetuses. Obstet Gynecol. 2009;113(5):10011007. 7 Whitlow BJ, Chatzipapas IK, Lazanakis ML, Kadir RA, Economides DL. The value of sonography in early pregnancy for the detection of fetal abnormalities in an unselected population. Br J Obstet Gynaecol. 1999;106(9):929936. 8 Saltvedt S, Almstrom H, Kublickas M, Valentin L, Grunewald C. Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation-a randomised controlled trial in 39,572 pregnancies. BJOG. 2006;113(6):664674. 9 Cargill Y, Morin L, Bly S, et al. Content of a complete routine second trimester obstetrical ultrasound examination and report. J Obstet Gynaecol Can. 2009;31(3):272275, 276280. 10 ACOG practice bulletin no. 101: Ultrasonography in pregnancy. Obstet Gynecol. 2009;113(2 Pt 1):451-461. 11 Bricker L, Neilson JP, Dowswell T. Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev. 2008(4):CD001451. 12 Crane JP, LeFevre ML, Winborn RC, et al. A randomized trial of prenatal ultrasonographic screening: impact on the

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detection, management, and outcome of anomalous fetuses. The RADIUS Study Group. Am J Obstet Gynecol. 1994;171(2): 392399. Society for Maternal Fetal Medicine (SMFM) CC. White paper on ultrasound code 76805. Society for Maternal Fetal Medicine, Washington, DC; 2012. ACR, ACOG, AIUM practice guidelines for the performande of obstetrical ultrasound. http://www.acr.org//media/F7BC35 BD59264E7CBE648F6D1BB8B8E2.pdf; 2007. Society for Maternal Fetal Medicine (SMFM) CC. White paper on ultrasound code 76811. Society for Maternal Fetal Medicine, Washington, DC; 2012. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357(5):462469. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, doubleblind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011;38(1):1831. The American Congress of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstetrics and gynecology 2012;120(4): 964-973.