Routine prenatal ultrasonography as a screening toolhttp://www.uptodate.com/contents/routine-prenatal-ultrasonography-as-a-screening-tool?source=search_result&search=ultrasonographic+on+pregnancy&selectedTitle=15%7E150#H23

Routine prenatal ultrasonography as a screening toolAuthorsAnna K Sfakianaki, MDJoshua Copel, MDSection EditorsCharles J Lockwood, MD, MHCMDeborah Levine, MDDeputy EditorVanessa A Barss, MD, FACOGDisclosures:Anna K Sfakianaki, MDNothing to disclose.Joshua Copel, MDNothing to disclose.Charles J Lockwood, MD, MHCMConsultant/Advisory Boards: Celula [Aneuploidy screening (Prenatal and cancer DNA screening tests in development)]. Equity Ownership/Stock Options: Celula [Aneuploidy screening (Prenatal and cancer DNA screening tests in development)].Deborah Levine, MDNothing to disclose.Vanessa A Barss, MD, FACOGNothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policyAll topics are updated as new evidence becomes available and ourpeer review processis complete.Literature review current through:Jun 2015.|This topic last updated:Jun 02, 2015.INTRODUCTIONPrenatal ultrasonography is a common procedure in many countries [1-4]. It is an accurate technique for determining gestational age, number of fetuses, fetal cardiac activity, and placental location. In addition, many congenital structural anomalies and significant abnormalities in fetal growth can be identified. However, whether all obstetrical patients should undergo ultrasound screening and whether such screening improves pregnancy outcome is controversial.Many countries have developed local guidelines for the practice of prenatal ultrasonography and most offer at least one mid-trimester ultrasound examination as part of standard prenatal care, although worldwide obstetric practice varies [5]. In the United States, the American College of Obstetricians and Gynecologists (ACOG) supports the use of ultrasound when there is a specific medical indication and advises against nonmedical use of prenatal ultrasonography (eg, to accommodate parental curiosity about fetal sex or parental desire to viewand/orobtain an image of the fetus) [6,7]. ACOG also stated that the benefits and limitations of ultrasonography should be discussed with all patients, and performance of the procedure is reasonable in patients who request it. In addition, a 2006 workshop organized by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) reached a consensus that all fetuses should have a screening ultrasonogram for the detection of fetal anomalies and pregnancy complications [8].An evidence-based discussion of the application of ultrasound to an unselected obstetric population as a screening tool will be presented here. The use of prenatal ultrasonography for specific obstetrical indications is reviewed separately. (See"Ultrasound examination in obstetrics and gynecology".)CRITERIA FOR A GOOD SCREENING TESTIn general, a good screening test should be safe, have high sensitivity and specificity, ideally take only a few minutes to perform, require minimum preparation by the patient, and be inexpensive. It should identify individuals with an important disease or condition and be cost-effective, allowing for control of health care costs by identifying disease early and treating before the consequences of the disease are overwhelming. (See"Evidence-based approach to prevention", section on 'Methodologic issues in evaluating screening programs'.)RATIONALE FOR ROUTINE SCREENING PRENATAL ULTRASOUNDIt is hypothesized that routine use of ultrasound in all pregnancies will prove beneficial since adverse outcomes may occur in pregnancies without risk factors and clinical conditions that place the fetus at high risk may not be detected by clinical examination. The primary objective is to obtain information that will enable delivery of optimal antenatal care and thus the best possible outcomes for mother and fetus [5]. However, the benefit of such prenatal sonographic screening on neonatal outcomes remains unproven.The components of a standard prenatal ultrasound examination are described in the tables (table 1andtable 2) and reviewed in detail separately. (See"Ultrasound examination in obstetrics and gynecology".)BENEFITS OF ROUTINE PRENATAL ULTRASOUND EXAMINATIONCompared to no prenatal ultrasound examination or ultrasound examination in selected patients, routine ultrasound examination improves:Estimation of gestational ageIdentification of multiple gestationIdentification of congenital anomaliesBetter estimate of gestational age/delivery dateDetermination of the expected date of delivery (EDD) is essential in obstetrics so that misdiagnosis (and inappropriate intervention) of previable, preterm, and postterm pregnancy can be avoided. As more focus is placed on reducing late preterm birth and early term birth, more accurate estimation of EDD takes on increasing importance. Ample evidence has accumulated that routine ultrasound examination results in more accurate assessment of the EDD than last menstrual period (LMP) dating or physical examination, even in women with regular and certain menstrual dates [9-11]. Prenatal assessment of gestational age and determination of EDD is discussed in detail separately. (See"Prenatal assessment of gestational age and estimated date of delivery".)The benefits of ensuring the most accurate estimation of gestationalage/deliverydate include a reduction in intervention for postterm pregnancy, reduction in diagnosis of fetal growth restriction, and reduction in use of tocolysis. More accurate estimation of EDD may also reduce planned cesarean delivery before 39 weeks of gestation resulting from misdiagnosis of gestational age.Reduction in intervention for postterm pregnancyUltrasound-based determination of EDD reduces intervention for postterm pregnancy. In a 2010 Cochrane review of 11 trials ofroutine/revealedultrasound versusselective/concealedultrasound before the 24th week of pregnancy, routine use of early ultrasound and the subsequent adjustment of the EDD led to a significant reduction in induction of labor for postterm pregnancy (RR 0.59, 95% CI 0.42-0.83) [11]. (See"Postterm pregnancy".)Although these trials showed that ultrasound determination of EDD as late as 24 weeks can reduce the number of pregnancies eventually diagnosed as postterm, as well as scans performed at 10 to 18 weeks, a randomized trial looking specifically at the timing of the examination demonstrated that first trimester ultrasound examination in a low-risk population was more effective than second trimester ultrasound examination in decreasing postterm pregnancy [12].Better detection of aneuploidySerum screening protocols are dependent upon accurate estimation of gestational age. The majority of abnormal tests recalculated based on corrected EDD are normal. Thus, routine ultrasound estimation of gestational age may reduce the number of women who have anxiety caused by false positive results in serum screening. (See'Better estimate of gestational age/delivery date'above and"Laboratory issues related to maternal serum screening for Down syndrome", section on 'Method of gestational age determination'.)In addition to gestational age determination, the combination of sonographic nuchal translucency measurement and maternal serum analyte assessment in the first trimester can detect over 90 percent of fetuses with Down syndrome, as well as some fetuses with other aneuploidies. (See"Sonographic findings associated with fetal aneuploidy"and"Down syndrome: Overview of prenatal screening"and"First trimester combined test and integrated tests for screening for Down syndrome and trisomy 18".)Risk assessment for fetal aneuploidy using cell-free DNA in maternal blood is not dependent on precise determination of gestational age. (See"Noninvasive prenatal testing using cell-free nucleic acids in maternal blood".)Better identification of multiple gestationA major benefit of routine ultrasound screening is early, reliable identification of twin pregnancies. In women who do not undergo routine ultrasound examination, a significant number of twin pregnancies are not recognized until the third trimester or delivery. (See"Twin pregnancy: Prenatal issues".)In the 2010 Cochrane review of trials of routine ultrasound before the 24th week of pregnancy described above, multiple gestation was diagnosed earlier in routinely scanned pregnancies and ultrasound in early pregnancy significantly reduced the failure to detect multiple pregnancy by 24 weeks of gestation (RR 0.07, 95% CI 0.03-0.17; 7 trials, 295 patients) [11]. In the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS), of over 15,000 gravidas (the largest trial in the Cochrane review), women who did not have a routine second trimester ultrasound examination had 38 percent of twin pregnancies unrecognized until after 26 weeks of gestation and 13 percent of twins were not diagnosed until delivery [13]. There were no twin pregnancies missed on ultrasound examination.Similar findings were reported by the Helsinki trial, a prospective randomized trial of 9310 women, of which 4691 underwent screening ultrasound between 16 and 20 weeks [14]. All twin pregnancies were detected before 21 weeks of gestation in the screened group, versus 76.3 percent in the control group. Moreover, the perinatal mortality rate (PMR) of twins in the screened group was 27.8/1000compared with 65.8/1000in the control group, although these were small numbers and did not reach statistical significance. Retrospective series have also suggested improved neonatal outcomes with early diagnosis of twin pregnancy [15].Better detection of congenital anomaliesThe ability of routine ultrasound screening to detect fetal anomalies in an unselected population is highly controversial. Over 30 studies have evaluated this question, and numerous reviews have attempted to summarize them critically [16]. In the 2010 Cochrane review of trials of routine ultrasound before the 24th week of pregnancy described above, performance ofroutine/revealedearly pregnancy ultrasound significantly increased detection of fetal abnormalities before 24 weeks of gestation (RR 3.46, 95% CI 1.67-7.14; 2 trials, 387 patients) [11]. A number of factors (eg, gestational age at examination, type of malformation, number of ultrasounds performed, operator experience, quality of equipment, population characteristics) affect detection rates, and were not addressed in the meta-analysis (see'Factors affecting detection rates'below).The largest trials and studies comparing second trimester screened and unscreened pregnancies are reviewed below (only RADIUS was included in the Cochrane review).Helsinki Trial The Helsinki Trial, performed from 1986 to 1987, randomly assigned 4691 women to screening ultrasound at 16 to 20 weeks to look for fetal anomalies and compared their outcome to 4619 controls who underwent ultrasound examination if obstetrically indicated [17]. Ultrasounds were performed at one of two hospitals, 95 percent of all pregnant women in the Helsinki metropolitan area agreed to participate, and only four women were lost to follow-up (but mortality data were complete). Seventy-seven percent of women in the control group underwent ultrasound examination sometime during pregnancy. Routine second trimester ultrasound screening resulted in:Significantly increased detection of fetal anomalies. The rate of detection of malformations was 36 percent in the City Hospital and 77 percent at the University Hospital.A significant reduction in the PMR (4.6/1000versus 9.0/1000in controls) because elective termination of anomalous fetuses resulted in fewer fetal and neonatal deaths due to congenital anomalies.RADIUS Trial The RADIUS trial was the first randomized trial of routine obstetrical ultrasound screening in the United States [13,18]. It included over 15,000 women randomly assigned to either screening ultrasounds at both 15 to 22 weeks and 31 to 35 weeks or to ultrasound for obstetrical indications only. Forty five percent of the control group had at least one ultrasound. Routine second trimester ultrasound screening resulted in:Significantly increased detection of fetal anomalies (34.8 versus 11 percent in controls). Of these anomalies, one-half were detected prior to 24 weeks of gestation in the screened group (16.6 percent of the total cohort of anomalous fetuses). As noted in the Helsinki trial, detection rates were significantly higher in tertiary facilities.No improvement in any perinatal outcome under study, including mortality, preterm birth, birth weight, and neonatal morbidity (retinopathy of prematurity, bronchopulmonary dysplasia, need for mechanical ventilation, necrotizing enterocolitis, intraventricular hemorrhage).No increase in the number of abortions performed for fetal anomalies, which was the same in both groups.No improvement in survival among anomalous fetuses. Antenatal detection of fetal anomalies did not improve survival over that with postnatal diagnosis.Eurofetus study The Eurofetus study of 1999 is the largest study of routine ultrasonographic examination in unselected population [19]. Women were routinely scanned by trained sonologists at 18 to 22 weeks in 61 centers across Europe. Major findings were:The sensitivity for detection of all anomalies was 56.2 percent.The detection rate was higher for major (73.7 percent) than for minor (45.7 percent) anomalies, and higher for anomalies of the central nervous system (CNS, 88.3 percent) and the urinary tract (88.5 percent) than for cardiac abnormalities (38.8 percent of major cardiac and 20.8 percent of minor cardiac anomalies were detected).Overall, 44 percent of anomalies and 55 percent of severe anomalies were detected before 24 weeks. Cardiac defects and cleftlip/palatewere diagnosed later in pregnancy than abnormalities of the CNS, urinary tract, or musculoskeletal systems.The rate of live births for mothers carrying fetuses with anomalies was lower than that of mothers carrying fetuses with no detected anomalies because many pregnancies with anomalous fetuses were electively terminated.Factors affecting detection ratesSeveral important factors need to be considered when analyzing these data: prevalence of anomalies, characteristics of the population, the setting in which the ultrasound was performed, and study design.Prevalence of anomalies Detection rates for anomalies are dependent upon the prevalence of each anomaly in the population studied, and prevalence is highly dependent upon the quality of follow-up achieved. For example, how thoroughly were aborted fetuses, stillbirths, and neonates examined for presence of anomalies? Were autopsies and x-rays performed when appropriate? Were neonates examined by a physician with additional expertise in dysmorphology? How many neonates underwent noninvasive studies with incidental discovery of a congenital anomaly? Some anomalies are not diagnosed until early childhood; was there examination of pediatric records to identify these children?

The table shows that anomaly prevalence rates reported in the literature range from 0.3 to 3.2 percent (table 3). Studies with low prevalence rates likely represent incomplete follow-up, thus detection rates and published sensitivities are not necessarily reliable. The last column in the table corrects for the differing prevalence rates and standardizes sensitivity rates for each study. The adjusted overall cumulative sensitivity becomes 40 percent, with the Eurofetus detection rate climbing to almost 70 percent.Population characteristics Characteristics of the population studied also affect both detection rates and the applicability of data to other populations. For example, two of the RADIUS trial's main inclusion criteria were that the patients have private obstetrical care and that they be indifferent to the possibility of termination of pregnancy. In fact, after all exclusions, only 28 percent of the eligible women actually participated in the study. One consequence of these selection criteria is that women who wished to undergo ultrasound examination, including those who might consider termination in the event of fetal anomaly, did not elect to participate. Thus, the observation that 71 percent of women with ultrasound-detected anomalies prior to 24 weeks decided to continue their pregnancies is not generalizable to an unselected population of pregnant women.

In this respect, data from the Helsinki trial, which included 95 percent of women in the area, more reliably describe the consequences of detecting fetal anomalies antenatally. The Helsinki trial reported that birth rates of anomalous fetuses were low due to termination of many of these pregnancies.

Another important aspect of the RADIUS trial is that approximately 85 percent of the population ultimately had an identifiable indication for ultrasound. Seventy percent of women were excluded prior to randomization, primarily because potential indications for ultrasound examination were present, and 50 percent of the remaining (enrolled) patients developed indications during the trial.Setting The setting in which the ultrasound is performed significantly affects detection rates. Factors relating to the setting involve the equipment available, as well as the skill and experience of the examiners. Both the RADIUS trial and the Helsinki trial showed that examinations performed in hospital or tertiary care settings identified more anomalies than those performed in office-based or community centers and ultrasound was more effective when performed by experienced operators. A review by the German Institute for Quality and Efficiency in Health Care (IQWiG) also noted that higher qualifications or greater experience of examiners and superior device quality were associated with higher detection rates for fetal abnormalities [20].

It is important to note that the RADIUS and Helsinki trials were both performed in the 1980s when ultrasound technology was still new. Since that time, the technology has evolved dramatically, which could enhance the diagnostic efficacy of less experienced sonologists and sonographers.Study design Studies are designed and powered to detect differences in their main outcome variables. Investigators choose study outcomes based upon their clinical significance and relevance to the question at hand. The endpoints chosen by the investigators of the RADIUS trial were associated with prematurity, rather than with anomalies and their consequences. RADIUS was not powered to detect differences in secondary outcome measures associated with the diagnosis of anomalies, such as impact on immediate survival, long-term neonatal outcomes in anomalous fetuses, and economic and social implications. In fact, the survival rate for infants with acute life-threatening anomalies was higher in the screened group (75 percent) than in the unscreened group (52 percent). Although this was not statistically significant, this was likely due to the very small sample size.

Other investigators have found that patients with cardiac anomalies [21] and specifically hypoplastic left heart [22] and transposition of the great arteries [23] have better outcomes when the diagnosis is made prenatally rather than postnatally. The data regarding long-term outcome for prenatally diagnosed anomalies of the renal system are conflicting and limited [24].First trimester screeningDetection of fetal anomalies in the first trimester is limited by the small size of the fetus and ongoing fetal development, which can result in later development of markers suggestive of an underlying abnormality (eg, hydramnios related to esophageal atresia). Nevertheless, ultrasound technology is rapidly progressing and assessment of fetal anatomy in the first trimester is becoming more widely available.A 2013 systematic review of the accuracy of ultrasonography at 11 to 14 weeks of gestation for detection of fetal structural anomalies included 19 observational studies, approximately 78,000 fetal anatomy examinations, and 996 postnatally-confirmed malformed fetuses [25]. The overall detection rate for fetal structural anomalies was 51 percent, but detection rates for specific abnormalities varied widely from 0 to 100 percent. For example, no cases of renal agenesis were detected in this gestational age range, fewer than 50 percent of cases of spina bifida were detected, more than 50 percent of cases of omphalocele, gastroschisis, and tetralogy of Fallot were detected, and 100 percent of anencephalic fetuses were detected. Detection of anomalies was more likely if there were multiple anomalies, both abdominal and vaginal ultrasound examination was performed, or the woman was at high risk. Although there was considerable heterogeneity among these studies, the findings affirm both the potential benefits and limitations of the first trimester fetal anatomic survey. Most women will need a second trimester survey to provide a more reliable assessment of fetal anatomy.The use of nuchal translucency measurement in the first trimester as a marker for the detection of congenital heart disease is discussed elsewhere. (See"First trimester cystic hygroma and increased nuchal translucency".)POTENTIAL BENEFIT OF ROUTINE SCREENINGPrevention of preterm birthA 2013 Cochrane review did not find sufficient evidence to recommend routine cervical length screening of all pregnant women [26]; however, the trials did not have a clear protocol for management of women based on cervical length and included heterogeneous populations. Based on a meta-analysis of five trials of progesterone treatment of women with asymptomatic midtrimester cervical shortening, cervical length screening for all singleton pregnancies in the midtrimester coupled with treatment of women found to have a short cervix is a reasonable approach [27]. (See"Second trimester evaluation of cervical length for prediction of spontaneous preterm birth", section on 'Guidelines from national organizations'.)In a 2012 practice bulletin, the American College of Obstetricians and Gynecologists (ACOG) neither mandated universal routine cervical length screening in women without a prior preterm birth nor recommended against such screening [28]. However, in women undergoing obstetrical ultrasound examination, ACOG has recommended that the cervix be examined when clinically appropriate and technically feasible [29]. In 2011, the Society of Obstetricians and Gynaecologists of Canada (SOGC) concluded that routine transvaginal cervical length assessment was not indicated in women at low risk [30].UNPROVEN OR UNCLEAR BENEFIT OF ROUTINE SCREENINGBetter diagnosis of deficient growth and improvement in perinatal outcomeAn early ultrasound examination serves as a key baseline against which later examinations are compared for the evaluation of fetal growth. The assessment of appropriate fetal or neonatal size is based upon the expected weight for gestational age. If gestational age is overestimated, then an appropriately grownfetus/neonatemay be incorrectly classified as growth restricted or small for gestational age (SGA). However, in the 2010 Cochrane review of trials ofroutine/revealedultrasound versusselective/concealedultrasound before the 24th week of pregnancy described above, routine use of early ultrasound did not result in a significant reduction in diagnosis of SGA (RR 1.05, 95% CI 0.81-1.35; 3 trials, 17,105 patients) [11]. (See"Fetal growth restriction: Diagnosis".)A late pregnancy screening ultrasound (third trimester) for fetal growth disturbance in low-risk women also has not been effective for reliably detecting these fetuses or improving outcome.In a 2008 Cochrane review of trials of routine ultrasound >24 weeks versusno/concealed/selectiveultrasound >24 weeks of gestation, routine ultrasound did not improve detection of neonates with birthweight