- Academic Editor
Background: Association between second trimester ultrasound
findings and twin pregnancy outcome is still unclear. Study aimed to evaluate the
performance of second trimester ultrasound scan in the prediction of
monochorionic diamniotic twin pregnancies outcomes. Methods:
Prospective-cohort study of all consecutive healthy women with monochorionic twin
pregnancies followed-up and delivered in five years was undertaken. During second
trimester screening (16–18 weeks) fetal biometry was measured (biparietal
diameter–BPD, abdominal circumference–AC, femur length–FL, estimated fetal
weight–EFW) and inter-twin discordance noted. Amniotic fluid amount was
determined. Pregnancy outcomes were having live-born twins, Apgar sores and
birth-weights, pregnancy complications and gestational week of delivery.
Results: Receiver operating characteristics (ROC) analysis showed that
BPD (p = 0.018), AC (p = 0.019) and FL (p = 0.015)
were good predictors of having live-born twins. Regression analysis showed that
the most important factors influencing twins’ survival to term were inter-twin
AC, BPD and FL differences. Fetal discordance in BPD, AC and FL explained
correctly 76.3%, 76.5% and 58% of pregnancy outcomes. If second trimester
inter-twin BPD difference was
Monochorionic twin pregnancies are considered to have a high risk of perinatal morbidity and mortality, mainly from fetal growth restriction and preterm birth [1, 2, 3]. Other complications and causes of fetal death in these pregnancies include fetal anomalies, twin-twin transfusion syndrome (TTTS), tight cord entanglement, twin reversed arterial perfusion (TRAP), and acute hemodynamic imbalances due to large placental vascular anastomoses [4, 5].
A priority in the management of monochorionic twin pregnancies is to identify patients at risk of adverse outcomes in order to offer appropriate and early intervention and to address any modifiable risk factors [1, 2, 3]. Current protocols suggest that monitoring monochorionic twins for potential complications should start from 16 weeks and should be repeated fortnightly until 24 weeks. At each ultrasound scan from 20 weeks, two or more biometric variables should be determined to estimate fetal weight discordance. Ultrasound scans should be performed at intervals of less than 28 days, and any difference in size between twins greater than 25% should be considered a clinically important indicator of intrauterine growth restriction. When discordant fetal growth is observed, patients should be referred to a tertiary-level fetal medical center [4, 5].
Numerous studies have determined that inter-twin discordance detected in the early months of pregnancy is associated not only with later growth restriction but also with adverse outcomes. However, first-trimester crown-rump length (CRL) discordance seems to be of limited value in predicting poor pregnancy outcomes, as it is biased toward identifying twin pregnancy losses occurring before 20 gestational weeks (GW) [1, 2, 3, 6].
On the other hand, the literature suggests that both disproportionate and proportionate fetal growth restriction may start in the second trimester, which may lead to poor perinatal outcomes . Antenatal measurement of fetal abdominal circumference has proven to be the most sensitive ultrasound index for the detection of disturbances in fetal growth. Nevertheless, the association between second-trimester ultrasound biometry and adverse pregnancy outcomes in monochorionic twins has still not been thoroughly investigated [1, 8].
Therefore, the aim of this study was to evaluate the performance of second-trimester ultrasound scans in the prediction of adverse perinatal outcomes in monochorionic diamniotic twin pregnancies.
A prospective cohort study was undertaken that included all consecutive monochorionic diamniotic twin pregnancies that were followed up and delivered during a five-year period (2010–2015) at the Clinic of Gynecology and Obstetrics Clinical Center of Serbia. There are currently no exact data on the prevalence of monochorionic diamniotic twins in Serbia, but in our clinic during the study period, their prevalence ranged from 0.1–0.4%. Twins’ monochorionicity and diamnionicity was diagnosed by ultrasound usually during the first pregnancy check-up and at latest during the first trimester screening (Double test). After confirmation of the condition (a single placental mass with a negative lambda sign and an intra-amniotic membrane thinner than 2 mm), patients were closely monitored throughout their pregnancy. Gestational age was calculated according to Negel’s rule and ultrasound biometric parameters. Medical history data, including the mothers’ age and parity, the presence of comorbidities, and the mode of current pregnancy conception (spontaneous or by assisted reproduction technologies) were recorded for each patient. Exclusion criteria for the study included miscarriage before the eighth gestational week, genetic disorders in the twins, and chronic diseases in the mothers (e.g., diabetes, hypertension, heart disease, connective tissue diseases, hematological diseases, etc.) that might impact the course and outcome of the pregnancy. All patients provided their written consent to participate in the study, which was approved by the institution’s Review Board (440/X-3).
At the 16th–18th GW, a second-trimester ultrasound was performed, during which,
for both twins, biometric measurements (i.e., biparietal diameter [BPD],
abdominal circumference [AC], and femur length [FL]) were established. These
measurements were used to determine the estimated fetal weight (EFW) of both
twins. To evaluate the discordance between twins in the second trimester, we
deducted the smaller/shorter value from the higher/longer value for each
biometric parameter. In this way, the precise difference between the twins’
biometric measures was obtained. Moreover, the deepest fluid pocket (DFP) was
measured and used to assess the amount of amniotic fluid (oligohydramnios: DFP
Patients received regular follow-ups until delivery, and all pregnancy complications, such as intrauterine growth restriction, twin-to-twin transfusion syndrome, miscarriage (before the 24th GW), and premature delivery (24th–36th GW) were noted. Ultrasound monitoring of twins was performed using an ACCUVIX V10 device (Samsung Medison, Seoul, Republic of Korea), with a 3.75-MHz abdominal and s 45-Hz vaginal probe. Ultrasound examinations were performed for all women by the same sonographer (study author SA).
The primary positive pregnancy outcome that was assessed was the birth of live
twins (one or both). Upon delivery, birth weight and Apgar sores were registered
for all twins. The gestational week of delivery was also recorded and used as an
additional measure of pregnancy outcome (term
Ultrasound data obtained for all twins in the second trimester were compared
with the evaluated pregnancy outcomes. Data were analyzed using descriptive
methods (percent, mean, standard deviation) and analytical statistics using IBM
SPSS version 20 (IBM Corp., Armonk, NY, USA) for Windows. The correlations
between ultrasound measurements and pregnancy outcomes were analyzed using
Spearman’s correlation coefficient. The significance of the differences between
the parameters of twins was analyzed with the chi-squared, analysis of variance
(ANOVA), and Kruskal–Wallis
Receiver operating characteristics (ROC) curve analysis was performed to set the cut-off values of the second-trimester ultrasound measures (the direct difference in BPD, AC, FL, and EFW between twins) that could impact pregnancy outcomes (live-born twins and delivery time) in our population. The parameters that explained a significant percentage of cases on ROC analysis were considered adequate predictors of having live-born twins. Inter-twin discordance in the second trimester was established if the difference in the biometric parameters between the larger and smaller twin was over the cut-off value determined by our ROC analysis. Finally, inter-twin differences in BPD, AC, FL, and EFW were categorized as under or over the cut-off value and were further assessed.
Univariate regression analysis was applied to evaluate and confirm the associations between monochorionic twin pregnancy outcomes (dependent variables: having live-born twins, week of gestation at delivery, birth weight, and the Apgar scores of twins) and the differences between the twins’ second trimester ultrasound measures (the independent variables were the same for all regression analyses: AC, BPD, FL, EFW) along with the twins’ amniotic fluid measurements.
The study included 39 healthy women with monochorionic diamniotic twin
pregnancies. The average age of the women was 30.85
|Parameters (No 39)||Minimum||Maximum||Mean||Standard Deviation|
|BPD twin 1 (mm)||24.00||52.00||35.08||6.19|
|BPD twin 2 (mm)||28.00||53.00||35.94||5.46|
|BPD direct difference||0.00||11.00||2.30||2.55|
|AC twin 1 (mm)||62.00||149.00||104.59||20.05|
|AC twin 2 (mm)||71.00||171.00||106.17||20.99|
|AC direct difference||0.00||65.00||11.45||15.75|
|FL twin 1 (mm)||13.00||32.00||19.99||4.26|
|FL twin 2 (mm)||16.00||32.00||20.35||3.74|
|FL direct difference||0.00||10.00||1.69||2.10|
|EFW twin 1 16–18 GW (gr)||100.00||192.00||136.46||23.83|
|EFW twin 2 16–18 GW (gr)||91.00||180.00||133.35||24.91|
|EFW direct difference||0.00||41.00||10.08||10.05|
|GW at birth (gr)||16.00||39.00||31.77||6.57|
|Twin 1 birth-weight (gr)||150.00||3100.00||1840.53||906.08|
|Twin 2 birth-weight (gr)||150.00||3100.00||1799.73||947.93|
|Twin 1 Apgar score||0.00||9.00||4.74||3.67|
|Twin 2 Apgar score||0.00||9.00||5.10||3.52|
Legend: BPD, biparietal diameter; AC, abdominal circumference; FL, femur length; GW, gestational week; EFW, estimated fetal weight.
Generally, no significant differences were found between first and second twins regarding their mean ultrasound measures in the second trimester (BPD p = 0.516; AC p = 0.735; FL p = 0.698; EFW p = 0.461) or between the twins’ birth weights (p = 0.849) or Apgar scores (p = 0.661) upon delivery.
The amount of amniotic fluid of the examined women was mostly adequate in the second trimester. There were a few cases of oligohydramnios and polyhydramnios, but polyhydramnios was more frequent than oligohydramnios in the second trimester.
Most twins were born live and without any complications (either diagnosed during pregnancy by ultrasound or upon birth). Out of 18 cases with complications, intrauterine growth restriction was registered in 14 (17.95%) fetuses, twin-to-twin transfusion syndrome in eight (20.51%) twin pairs, chorioamnionitis in six (15.38%), and preterm birth in eight (20.51%) pregnancies. No other complications, such as TRAP or vanishing twins, were noted.
Based on the ROC analysis, it was found that BPD, AC, and FL inter-twin differences between the 16th and 18th GW could be used as predictors of having live-born twins, while a second-trimester inter-twin difference in EFW was not proven to be a reliable indicator of pregnancy outcome. Moreover, raw measures of BPD, AC, and FL in both the first and second twin were also not significant. However, the EFW measure of both twins, assessed separately, was significantly associated with the twins’ outcomes (Table 2).
|Parameters (No 39)||Area under ROC %||p||Cut-off values in mm/gr||Sensitivity %||Specificity %|
|BPD twin 1||59.6||0.386||33.5||56.7||44.4|
|BPD twin 2||59.6||0.386||33.5||70.0||44.4|
|BPD direct difference||76.3||0.018||2.5||66.7||80.0|
|FL twin 1||77.0||0.199||18.3||70.0||65.0|
|FL twin 2||64.3||0.474||18.5||70.0||66.7|
|FL direct difference||58.0||0.015||1.5||44.4||63.3|
|AC twin 1||56.7||0.549||95.0||73.0||44.4|
|AC twin 2||58.5||0.443||95.0||70.0||44.4|
|AC direct difference||76.5||0.019||17.0||55.6||96.7|
|EFW twin 1 grams||80.4||0.006||130.0||60.0||77.8|
|EFW twin 2 grams||84.8||0.002||120.5||73.3||77.8|
|EFW direct difference||45.4||0.677||5.5||53.3||44.4|
Legend: BPD, biparietal diameter; AC, abdominal circumference; FL, femur length; EFW, estimated fetal weight.
Consequently, cut-off values for BPD, AC, and FL inter-twin differences for our population were established (2.5 mm, 17 mm, and 1.5 mm respectively). BPD, AC, and FL difference categories (under cut-off = adequate twin growth vs. over cut-off = discordant growth) accurately predicted the risk for adverse pregnancy outcomes in 76.3%, 76.5%, and 58.0% of the cases, respectively.
When these new biometry categories were further analyzed, it was seen that our
sample contained significantly more twin pairs with a BPD difference of
|Parameters (No 39)||Frequency||%||p|
|BPD difference new categories||27||69.2||5.769||0.016|
|AC difference new categories||33||84.6||18.692||0.001|
|FL difference new categories||24||61.5||2.077||0.150|
|Amniotic fluid of twins||normal||30||76.9||35.231||0.001|
|Live-born twins||no–both twins||8||20.5||11.308||0.001|
|yes–both live born||30||76.9|
Legend: BPD, biparietal diameter; AC, abdominal circumference; FL, femur length; ART, assisted reproduction techniques.
Having both twins born live significantly was negatively correlated with the
amount of amniotic fluid and direct differences in the twins’ BPD and AC, as well
as with the BPD, AC, and FL difference categories (i.e., under or over
the cut-off value), while it was positively correlated with the FL and EFW of
both twins. Better survival of monochorionic twins was achieved when the
inter-twin difference in BPD was
In cases where the difference in AC between the twins was about 17 mm, 29 twins
were born live, but still there were cases of intra uterine fetal death. On the
other hand, when the difference in AC between the twins in the second trimester
The time of delivery was significantly negatively correlated with direct
differences between the twins’ BPD and AC, as well as the AC and FL difference
categories (i.e., under or over the cut-off) and was positively
correlated with the twins’ EFW. Delivery occurred in later gestational weeks when
the second-trimester inter-twin difference in BPD was
The Apgar scores of the twins were significantly negatively correlated with the
amount of amniotic fluid, the direct difference between the twins’ AC, and the AC
difference categories (i.e., above or below the cut-off) and were
positively correlated with the EFW of the smaller twin. Monochorionic twins with
a second-trimester inter-twin AC difference
Twins’ birth weights were significantly negatively correlated with the amount of
amniotic fluid, the direct difference between the twins’ AC, and the AC
difference categories (i.e., above or below the cut-off) and were
positively correlated with the twins’ EFW. The twins had higher birth weights
when the AC difference between them in the second trimester was
Having complications during pregnancy correlated positively amniotic fluid, with AC difference categories, BPD and FL direct difference and difference in FL categories, and negatively with EFW of twins in the second trimester. The twins had fewer complications when the second-trimester inter-twin difference in BPD was about 2.5 mm, in AC was about 17 mm, and in FL was about 1.5 mm. Twins with a higher weight at 16–18 GW had fewer pregnancy complications.
Neither the mothers’ age nor parity had a significant influence on any evaluated pregnancy outcome. Twins delivered by caesarean section had a better outcome. Table 4 shows the correlations between the second-trimester ultrasound twin measures and the evaluated pregnancy outcomes.
|Parameters (No 39)||Live-born twins||GW||Apgar twin 1||Apgar twin 2||Twin 1 BW||Twin 2 BW||Complic|
|AC twin 1||–0.062||0.097||–0.051||–0.110||–0.144||–0.227||0.098|
|AC twin 2||0.035||0.124||0.042||0.003||–0.091||0.005||–0.053|
|AC direct difference||–0.468||–0.389||–0.518||–0.372||–0.349||–0.371||0.241|
|AC new categories||–0.534||–0.610||–0.507||–0.540||–0.466||–0.453||0.461|
|BPD twin 1||–0.030||0.141||–0.047||–0.101||–0.095||–0.130||0.009|
|BPD twin 2||0.014||0.141||0.023||–0.038||–0.048||0.089||0.039|
|BPD direct difference||–0.395||–0.361||–0.230||–0.239||–0.382||–0.321||0.360|
|BPD new categories||–0.426||–0.191||–0.241||–0.195||–0.289||–0.163||0.386|
|FL twin 1||0.126||0.397||0.142||0.064||0.046||–0.010||–0.140|
|FL twin 2||0.059||0.399||0.064||–0.023||–0.116||0.027||–0.120|
|FL direct difference||–0.327||–0.120||–0.152||–0.185||–0.267||–0.226||0.339|
|FL new categories||–0.226||–0,267||–0.093||–0.114||–0.179||–0.135||0.520|
|EFW twin 1||0.444||0.503||0.268||0.298||0.482||0.405||–0.482|
|EFW twin 2||0.509||0.491||0.318||0.323||0.417||0.337||–0.487|
|EFW direct difference||–0.068||–0.053||–0.073||–0.150||–0.081||–0.173||0.190|
|Amniotic fluid of twins||–0.536||–0.262||–0.391||–0.486||–0.540||–0.589||0.471|
Legend: Complic, complications; AC, abdominal circumference; BPD, biparietal diameter; FL, femur length; EFW, estimated fetal weight; GW, gestational week; BW, birth weight.
After finding numerous significant correlations between the examined parameters and pregnancy outcomes, univariate regression analysis was performed to assess the use of second-trimester ultrasound parameters to predict monochorionic diamniotic twin pregnancy outcomes. Tables 5,6 show the significant ultrasound parameters confirmed by the univariable regression analysis. No significant associations were found for twins’ birth weight and Apgar sores.
|Parameters||Coefficient B||Coefficient Wald||p||Odds ratio||95% confidence interval for odds ratio|
|Lower bound||Upper bound|
|AC direct difference||–0.073||5.812||0.016||0.930||0.876||0.986|
|AC new categories||–3.590||8.684||0.003||0.028||0.003||0.300|
|BPD new categories||–2.079||6.105||0.013||0.125||0.024||0.651|
|FL new categories||–0.362||4.725||0.030||0.696||0.502||0.965|
Legend: AC, abdominal circumference; BPD, biparietal diameter; FL, femur length.
|Parameters||Unstandardized coefficients||Standardized coefficients||p||95% confidence interval for B|
|B||Standard error||Beta||Lower bound||Upper bound|
|AC direct difference||–0.242||0.056||–0.579||0.001||–0.355||–0.128|
|AC new categories||–11.152||2.318||–0.620||0.001||–15.849||–6.454|
|BPD direct difference||–1.209||0.374||–0.470||0.003||–1.967||–0.452|
|BPD new categories||–4.722||2.176||–0.336||0.037||–9.132||–0.313|
|FL new categories||–0.994||0.487||–0.318||0.049||–1.982||–0.006|
Legend: AC, abdominal circumference; BPD, biparietal diameter; FL, femur length.
Based on the obtained regression findings, it could be seen that direct difference in twins’ AC as well as difference of twins’ AC, BPD and FL according to newly set cut-offs were the most important predictors of having live-born twins. Moreover, direct differences in twins’ AC and BPD as well as differences in twins’ AC, BPD, and FL according to the newly set cut-offs were the most important predictors of gestational week of delivery. No other significant associations between second-trimester ultrasound parameters and pregnancy outcomes were confirmed by our regression analysis.
Recently, attention has been drawn to the use of early-second-trimester ultrasound examinations to predict adverse perinatal outcomes . Abnormal biometry has been confirmed in the literature as an independent contributor to the poor prognosis of twins. Moreover, it seems that ultrasound parameters have better predictive ability in monochorionic twins . Based on the available literature, the current study is one of the few that have investigated the ability of second-trimester ultrasound parameters to predict outcomes in monochorionic diamniotic twin pregnancies.
It is well known that a suboptimal environment in early pregnancy may limit growth during the second and third trimesters [6, 8]. It has been postulated that fetuses suffering from nutrient limitation during early pregnancy tend to be proportionately small at birth. Conversely, if growth restriction begins later in pregnancy due to pregnancy complications, fetuses are usually of normal length but lack adequate fat tissue deposits [11, 12]. Some authors consider that fetuses that are smaller than expected at the mid-second-trimester ultrasound screening are likely already suffering from early growth restriction .
Discordant growth between twins can be one of the signs of pregnancy complications that begin in the first half of pregnancy [9, 10]. A strong link between intrauterine growth restriction and TTTS or stillbirth has been found in numerous studies. These findings provide a rationale for using second-trimester fetal discordance to predict adverse outcomes [6, 13]. Nevertheless, only a few previous studies have focused on the role of biometry discordance, assessed either by expected fetal weight or abdominal circumference measured at the time of the routine anomaly scan in the second trimester, in twin pregnancy outcomes [1, 14]. Some studies indicate that a single biometric assessment of twins at 16 weeks detected 48% of later adverse outcomes. AC and EFW at 16 GW have been established as the most important predictors of adverse fetal outcomes as well as discordant twin growth [7, 12, 13].
One group of studies indicates that asymmetrically grown and discordant twins
have worse perinatal outcomes (preterm birth and perinatal death) than symmetric
twins [4, 9]. Previous studies have reported that
Conversely, other studies have found that second-trimester ultrasound
discordance in twins has poor predictive value for adverse perinatal outcomes,
irrespective of chorionicity [1, 18, 19, 20]. Although in some investigations,
second-trimester EFW discordance correlated with birth-weight discordance
The findings of our study are in accordance with the findings of previous studies that the biometric parameters of twins at 16 to 18 GW could be used as predictors of having live-born twins [1, 6, 11]. Inter-twin differences in BPD, AC, and FL detected early in the second trimester reliably predict pregnancy outcomes.
The cut-off for AC inter-twin difference in our sample corresponds with value
suggested in the literature (17 mm) [2, 13]. However, ours is the first study to
establish a cut-off value for BPD and FL inter-twin differences. In our study,
fetal discordance correctly predicted the risk of adverse pregnancy outcomes in
more than 50% of the twins. Nevertheless, it should be noted that the
sensitivity of all these measurements was not high. On the other hand,
discordance in AC and BPD was
According to our regression analysis, the most important predictors of having two live-born monochorionic twins were inter-twin AC, BPD, and FL differences categorized according to our newly proposed cut-off values. Our findings indicate that when the second-trimester inter-twin AC difference was about 17 mm, BPD was about 2.5 mm, and the difference in FL was about 1.5 mm, the survival of both twins was more likely, and delivery was more likely to occur closer to term. Thus, the discordant growth of twins in the second trimester was confirmed to correlate with adverse pregnancy outcomes.
The major limitation of our study is the small sample size, which impacts the generalizability and statistical relevance of the results. Moreover, our conclusions could be biased because the study did not include a control group. However, monochorionic twin pregnancies are quite rare compared to other pregnancy types. Therefore, the post-hock power of the study was good (71.2%). We plan to conduct further studies with larger samples in clinical practice to construct multivariable models for predicting the outcomes of monochorionic diamniotic twin pregnancy. Due to the rarity of of monochorionic diamniotic twins and consequently information regarding them our data would be useful for being assessed in an individual patient meta-analysis.
Discordant growth of twins along with amniotic fluid disturbances registered on
the second trimester ultrasound scan can be used as reliable sign of potential
adverse outcomes of monochorionic diamniotic twins. According to regression
analysis performed in our study inter-twin AC, BPD and FL differences are
biometric parameters of most importance when assessing monochorionic diamniotic
twins. If second trimester amniotic fluid is adequate, inter-twin BPD difference
The data presented in this study are available on request from the corresponding author, but not publicly available as we present personal patients’ findings.
SA, DKB and IB designed the research study. SA, JD and DKB analyzed the data. MMC, IV, MM and SM performed the research, interpreted the findings and performed the literature review. SA, DKB, JD, IV wrote the manuscript. SP and SB critically revised the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
All investigated women signed informed consent for the study. The study was approved by the Review Board of Medical Faculty University of Belgrade (440/X-3).
This research received no external funding.
The authors declare no conflict of interest.
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