First-trimester prediction of small-for-gestational age in pregnancies at false-positive high or intermediate risk for fetal aneuploidy.

OBJECTIVES: To explore the risk of small-for-gestational age (SGA) and fetal growth restriction (FGR) and to test the performance of first-trimester screening for SGA and FGR in women with a false-positive high or intermediate risk for aneuploidy. METHODS: This was a prospective cohort study of women with a singleton pregnancy attending for a routine first-trimester scan. The risks of aneuploidy and preterm SGA (defined as birth weight < 10th percentile with delivery before 37 weeks) were determined according to Fetal Medicine Foundation algorithms. In non-malformed euploid pregnancies, the predictive performance of both the aneuploidy and preterm SGA risks was evaluated for SGA, FGR (defined as birth weight < 3rd centile), preterm SGA and early SGA (delivery before 34 weeks), using receiver-operating-characteristics (ROC) curve analysis, in those with a high or intermediate risk of aneuploidy and in the overall population. RESULTS: A total of 2053 pregnancies were included in the analysis, of which 191 (9.3%) were at high or intermediate risk for aneuploidy (≥ 1/1000) and 304 (14.8%) were at high risk for preterm SGA (≥ 1/100). In total, there were 140 (6.8%) cases of SGA, 61 (3.0%) of FGR, 44 (2.1%) of preterm SGA and 33 (1.6%) of early SGA. Among women with a false-positive high or intermediate risk for aneuploidy, the rates of SGA, FGR, preterm SGA and early SGA were 13.6% (26/191), 7.9 % (15/191), 6.8% (13/191) and 5.8% (11/191), respectively. Compared with women with a first-trimester low risk for preterm SGA, regardless of aneuploidy risk, those with a high risk for preterm SGA and a high or intermediate risk for aneuploidy had relative risks for SGA, FGR, preterm SGA and early SGA of 6 (95% CI, 3.9-9), 9.2 (95% CI, 5.1-16.5), 13.4 (95% CI, 6.9-26.1) and 17.6 (95% CI, 8.1-38.2), respectively. The predictive performance for SGA of the preterm SGA algorithm was higher in women at high or intermediate risk for aneuploidy than in the overall population (area under the ROC curve (AUC), 0.8 vs 0.7; P < 0.001). Among women at high or intermediate risk for aneuploidy, the predictive performance of the preterm SGA algorithm was better than that of the aneuploidy algorithm for SGA (AUC, 0.80 vs 0.58; P = 0.003), preterm SGA (AUC, 0.85 vs 0.65; P = 0.013) and early SGA (AUC, 0.86 vs 0.60; P = 0.002). CONCLUSION: In women with a first-trimester false-positive high or intermediate risk of aneuploidy, further screening for SGA allows stratification of the risk for fetal growth disorders. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Assessment of cardiac angle in fetuses with congenital heart disease at risk of 22q11.2 deletion.

OBJECTIVES: To evaluate fetal cardiac angle as a screening tool for 22q11.2 deletion among cases with cardiac anomalies known to be associated with this genetic condition, to examine the correlation of fetal cardiac angle with thymic-thoracic (TT)-ratio, and to assess the performance of TT ratio as a covariate in screening for 22q11.2 deletion. METHODS: This was a retrospective cohort study that reviewed the records of 74 cases with cardiac anomalies known to be associated with 22q11.2 deletion (tetralogy of Fallot, common arterial trunk, interrupted aortic arch and right aortic arch) that were diagnosed between 2007 and 2013. The karyotype was known in all cases. The fetal cardiac angle and TT-ratio were measured using stored three-dimensional spatiotemporal image correlation volume datasets and compared in those with del.22q11.2 and those without. RESULTS: Of the 74 cases reviewed, 16 had 22q11.2 deletion. The mean cardiac angle was larger in the cases with 22q11.2 deletion than in those without (68.6° vs 58.7°, respectively; P = 0.02). Multivariate regression analysis showed an association between cardiac angle and TT-ratio in fetuses with 22q11.2 deletion (r(2) = 0.33; P = 0.02) but not in those with a normal karyotype (P = 0.4). Logistic regression analysis demonstrated that fetal cardiac angle, but not TT-ratio, is an independent predictor of 22q11.2 deletion among fetuses with 22q11.2 deletion-associated cardiac anomalies (P = 0.02; area under the receiver-operating characteristics curve = 0.69). CONCLUSIONS: An enlarged fetal cardiac angle is an independent predictor of 22q11.2 deletion among fetuses with 22q11.2 deletion-associated cardiac anomalies. However, its performance as a single variable in a screening model is not sufficient to guide management decisions regarding invasive testing.

Reliability of fetal thymus measurement in prediction of 22q11.2 deletion: a retrospective study using four-dimensional spatiotemporal image correlation volumes.

OBJECTIVES: To evaluate the thymic-thoracic ratio (TT-ratio) method in assessment of the fetal thymus in normal fetuses and in those with cardiac abnormalities, in the presence or absence of 22q11.2 deletion. METHOD: Database records were reviewed for cases of conotruncal and arch abnormalities found on fetal echocardiography between January 2007 and September 2011. The 22q11.2 deletion status was retrieved and cases in which this was not known were excluded from the analysis, as were fetuses with aneuploidy or other genetic disorders. An additional 55 normal fetuses were analyzed as a control group. The TT-ratio was measured retrospectively using stored spatiotemporal image correlation (STIC) volume datasets. RESULTS: Sixty-nine fetuses with relevant cardiac diagnoses were identified and, of these, 18 (26%) had 22q11.2 deletion. The mean gestational age at diagnosis was 22 weeks. Significant pairwise differences, but also overlap, were observed between all three groups (i.e. fetuses with heart defects with and without the 22q11.2 deletion and controls). The mean TT-ratio was 0.44 in our normal control group and was significantly smaller in fetuses with 22q11.2 deletion, corresponding to previously published data. However, the mean TT-ratio in the group with conotruncal anomalies but without the 22q11.2 deletion was also smaller than that in controls, in contrast to previously published data. The TT-ratio was above the normal mean, regardless of fetal karyotype, in all cases of interrupted aortic arch. CONCLUSION: The TT-ratio method is a feasible and potentially useful tool during detailed fetal heart assessment. However, the absolute measurement is not reliable for prediction of 22q11.2 deletion and the obtained results should therefore be interpreted with caution. Fetal karyotyping should be recommended in cases with conotruncal heart abnormalities, irrespective of the TT-ratio.