Target condition being diagnosed

Birth weight discordance (BWD), defined as a difference in the birth weights of twins, is a well‐documented phenomenon in twin pregnancies (Bagchi 2006; Mahony 2006). Estimated fetal weight discordance (EFWD) estimated by ultrasound is measured using the formula: ((larger twin estimated weight – smaller twin estimated weight)/larger twin estimated weight) × 100. EFWD of 20% or greater has been shown to have significant impact on fetal and perinatal outcomes. Growth discordance may occur as a physiological BWD, when both twins are appropriate‐for‐gestational‐age, or as pathological BWD when at least one twin is small‐for‐gestational age (Appleton 2007).

BWD is one of the major risk factors for adverse fetal, neonatal and maternal outcomes (Demissie 2002; Kilic 2006; Wen 2006). Demissie and colleagues found that the odds ratio of fetal death varied from 1.26 to 12.75 and the odds ratio of neonatal death varied from 1.02 to 3.43, depending on the degree of BWD. Kilic and colleagues reported higher frequency of mortality, sepsis, polycythaemia, hypoglycaemia, anaemia and respiratory distress syndrome among discordant twins. Wen and coworkers reported higher odds of maternal hypertension, eclampsia and other medical complications associated with BWD. Depending on the chorionicity, degree of discordance and the threshold used, BWD occurs in about 15% to 30% of twin gestations (Lewi 2008; Lopriore 2012; Miller 2012). Fetal growth abnormalities are associated with multiple conditions that affect fetal or neonatal well‐being, such as twin‐to‐twin transfusion syndrome (TTTS), chromosomal aberrations or structural defects. Excluding these conditions, discordant growth by itself is recognized as an independent risk factor for adverse perinatal outcomes (Mazhar 2010; Morin 2011; Suzuki 2009). BWD of 20% and 25% are the most common thresholds used in the literature to identify adverse perinatal outcomes (Jahanfar 2016a). One study suggested that BWD of 30% and greater is significantly associated with adverse perinatal outcomes irrespective of chorionicity (Jahanfar 2016b).

Several mechanisms have been proposed for growth discordance of fetuses exposed to the same intrauterine environment (Victoria 2001). For monochorionic (MC) twin pregnancies, the mechanism is explained through conditions such as TTTS and intrauterine growth retardation (IUGR). These two conditions result in greater risk of fetal and neonatal mortality compared to dichorionic (DC) twins. Technology is available to manage TTTS including amnio‐reduction and septotomy (Behrendt 2016), hence monitoring is usually started as early as 20 weeks.

In the case of DC twin pregnancies, intrauterine growth restriction and placenta pathology can cause growth discordance. Abnormal cord insertion and insufficient placental implantation in the uterine wall are other proposed mechanisms for BWD. These conditions are non‐treatable; hence, the main management is to determine fetal well‐being and decide the optimal time for delivery to save the growth discordant twins.

If the accuracy of ultrasound in assessing the 20% to 25% cut‐off is known, it helps the complex decision making that the clinician goes through in deciding whether to intervene medically (via laser photo coagulation) or deliver the twins to avoid fetal morbidities or even death.

Index test(s)

Ultrasound has been an important tool in the diagnosis of BWD since 1972 (Hoopmann 2011; Woo 1939). Diagnostic ultrasound is a sophisticated electronic technology, which utilizes pulses of high‐frequency sound to produce an image. In the past, before ultrasound became available, abdominal palpation was used, which is extremely poor for detecting growth discordance. Radiological examination is not recommended since it is not safe for the fetus.

Diagnosis of EFWD can be made via two modalities of ultrasound.

1. A series of diagnostic two‐dimensional (2D) ultrasound examinations is used to assess fetal growth of both twins; identify chorionicity; and diagnose problems with cord, amnion layers, congenital abnormalities and TTTS. Doppler ultrasound is used to detect abnormal blood flow patterns in fetal/placenta circulation which may indicate poor fetal prognosis (Alfirevic 2003).

2. Three‐dimensional (3D) ultrasound to facilitate the assessment of the placenta, such as surface‐rendered imaging and volume measurement, quantitative and qualitative assessments of the vascularization, and blood flow of the placenta (Hata 2011).

The standard diagnostic test for fetal growth discordance is ultrasound. Growth discordance can be estimated by measuring crown rump length (CRL: the distance measured from the top of the head to the bottom of the buttocks) at or before 12 weeks of gestation (Tai 2007). Later, during the second and third trimesters, other ultrasound measures such as biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) are used to estimate fetal weight and calculate the degree of BWD (Simoes 2011).

It is still unclear whether first or second trimester findings can accurately predict BWD, what sonographic parameters assessed at each trimester are reliable to assess for discordance or whether any particular ultrasound modality (e.g. 2D or 3D) is superior to the other.

Apart from EFWD, information on chorionicity is essential for the management of a twin pregnancy for the following reasons.

1. MC twins are at greater risk of fetal morbidity and mortality due to shared vascularization.

2. If monochorionicity is suspected at early ultrasound screening, subsequent screening should be serially scheduled during the second and third trimester.

Early ultrasound detection narrows down the differential diagnosis for the underlying causes such as placenta sharing and subsequent vascular anastomosis as an underlying cause of EFWD. Better prognosis is expected for DC twin pregnancies as they do not share placentas (Miller 2012). In simpler terms, MC twins have higher risk of complications and should be assessed separately.

Second trimester ultrasound screening, from 16 to 24 weeks' gestation is useful in measuring AC, amniotic fluid pockets, identification of dividing membrane between amniotic sacs and umbilical artery Doppler studies (Giles 1998; Rizzo 1993).

Third trimester ultrasound, after 24 weeks' gestation, aims at identifying discordance or insufficient fetal growth. Identification of a discordant twin is crucial if one of the twin pairs is small‐for‐gestational age rather than both being appropriate‐for‐gestational‐age.

It should be noted that there is overlap in the use of these diagnostic tests from one trimester to another.

The standard of practice is to identify the growth discordance in twin pregnancies using ultrasound (2D or 3D, or both) using measurements (CRL, BPD, AC or FL) in either early (for CRL) or late pregnancy (for BPD, AC and FL) and compare with the actual birth weight. Since EFWD of 20% and 25% are associated with adverse perinatal outcomes, we studied the diagnostic accuracy of ultrasound at those threshold values.

Clinical pathway

In the management of a twin pregnancy, evaluation of fetal growth is particularly important because growth restriction and prematurity are major causes of morbidity and mortality reported in twins compared with a singleton pregnancy (Adegbite 2004). Most clinicians start monitoring MC twins for growth delay and discordant growth from 18 weeks' gestation every two to three weeks. Each twin's growth, amniotic volume and fetal bladder volume are monitored for signs of oligohydramnios or polyhydramnios. in contrast, in DC twins, fetal growth monitoring by ultrasound usually begins after 20 weeks of gestation every four to six weeks as fetal growth deceleration leading to discordance is optimally detected between 20 and 28 weeks of gestation (Gonzalez‐Quintero 2003).

When discordant growth is identified in the absence of TTTS or congenital abnormalities, intensive fetal monitoring of fetal well‐being is employed until delivery becomes indicated. In mildly discordant twins, expectant management by frequent fetal assessment is preferable to preterm delivery, given the limitation of ultrasound diagnosis of growth discordance. In one large non‐randomized study of 2399 twin pregnancies, the sonographic diagnosis of discordance greater than 25% was a poor predictor of BWD, fetal loss after 22 weeks' and 28 weeks' gestation, perinatal death and preterm birth before 34 weeks of gestation (D'Antonio 2014). In complicated twin pregnancies, in particular those with fetal growth restriction and discordant growth, fetal well‐being assessment by a non‐stress test (NST), biophysical profile (BPP), amniotic fluid index (AFI) measurement and Doppler velocimetry may be useful to identify which fetuses would benefit from early delivery (Devoe 1995).

Ideally, a diagnostic test is expected to correctly identify all patients with the assessed condition and to exclude all patients without it; that is, to have a sensitivity and specificity of 100%. In practice, however, it is extremely rare to find a test with equally high sensitivity and specificity, when compared to the current gold standard (BWD). For most tests, there is usually a trade‐off between the measures. An approach to the test might vary depending on the clinical context, which relates to the consequences of missed diagnosis and magnitude of subsequent interventions if the test is positive. If clinical priority would be to avoid missed diagnosis, an adequate test in that case would be expected to have a high sensitivity (low false‐negative results), with lower specificity (higher number of false‐positive results). Thus, no woman with a growth discordant twin pregnancy is missed by a test, but some still get unnecessary interventions (intensive surveillance, early delivery, consequential issues pertaining to prematurity such as admission to the neonatal intensive care unit, costs associated with care for the premature baby and increased distress for parents). An alternative approach gives priority to a test that avoids unnecessary invasive interventions. In this scenario, the emphasis should be on a high specificity (close to 100%) with lower sensitivity (preferably above 50%), which will rule out growth discordance of the twins, but will not detect some women with this condition. Ruling out growth discordance eliminates the need for further clinical intervention. Ideally, a test with high sensitivity and specificity is most useful in a clinical setting, which will help in efficient patient counselling and ongoing pregnancy management. Improving the selection of patients who might benefit from interventions such as laser coagulation or amnioreduction or early delivery would be of considerable benefit to neonates, mothers, families and the community.

Rationale

Guidelines provide conflicting advice about the time, frequency and type of ultrasound measurements that reliably diagnose growth discordance. According to the American College of Obstetricians and Gynecologists (ACOG), growth discordance is defined as a difference of AC of 20 mm or estimated fetal weight (EFW) difference of 20% (ACOG Committee 2004). The Society of Obstetricians and Gynecologists of Canada recommends that the EFW be derived from bi‐parietal diameter with AC or a combination of AC and FL (Okun 2000). ACOG does not provide recommendations on the frequency of ultrasound examinations for twins while the green guideline from the Royal College of Obstetricians and Gynecologists advocates screening ultrasound for MC twins every two to three weeks from 16 weeks’ gestation onwards (NICE 2011).

For DC twins, the issues related to feto‐placental perfusion leading to growth discordance can be clarified by screening ultrasound. However, there are no guidelines on the optimal gestation at which to start screening, or the frequency and gestations for subsequent screenings. Moreover, gender is an important factor that has interaction with BWD and perinatal outcomes (Melamed 2009; Miller 2012). Identifying the gender mix by ultrasound improves predictability of antenatal outcomes (Di 2007). Thus, the accuracy of ultrasound to identify gender is also crucial. As a part of this review, we investigated the impact of gender on BWD as a confounding factor.

The variation in recommendations made in the guidelines arises from the fact that the ability to estimate abnormal growth is challenging. It is not clear if the antenatal prediction of a critical BWD by fetal weight estimation formulae ((birth weight of heavier twin – birth weight of lighter twin)/birth weight of heavier twin) two to three weeks prior to delivery (Caravello 1997), provides an accurate estimation of BWD (Kalish 2003; Klam 2003; van Mieghem 2009). The pooled sensitivity for ultrasound prediction of BWD of 25% or greater, in three studies, was 63% for a false‐positive rate of 2% (Caravello 1997; Diaz‐Garcia 2010; Gernt 2001).

The existing uncertainties are further complicated by an inconclusive predictive value of early (first‐second trimester) versus late detection (two to three weeks prior to delivery) of growth discordance, use of different sonographic estimates (AC versus FL), and reliance on the retrospective nature of study designs and small sample sizes of existing literature. Literature suggests that biometric measurements of EFWD at early gestation or during the second trimester have significantly different precisions (Banks 2008; Tai 2007). Moreover, the efficacy of a single biometric measurement, such as CRL or AC with or without other measurement(s), in predicting BWD, is controversial (Banks 2008; Bhide 2009; Chamberlain 1991; Chitkara 1985). The most popular current methods for predicting discordant growth in twin gestations have limited accuracy when held to a standard for discordance that requires a birth weight difference of at least 20% (Caravello 1997), as sonography tends to underestimate the degree of discordance (Chang 2006).

We reviewed and summarized the evidence for the diagnostic accuracy of antenatal ultrasound for EFWD compared to the BWD to inform clinical practice.