Increased nuchal translucency before 11 weeks of gestation: Reason for referral?

OBJECTIVES: In this era of non-invasive-prenatal testing (NIPT), when dating scans are usually performed around 10 weeks of gestation, an increased NT before the official established timeframe (CRL between 45 and 84 mm) may be encountered. Information on management of these pregnancies is limited. Therefore, we evaluated the relationship between an early increased NT and adverse pregnancy outcome. Secondary, we evaluated the rate of chromosomal anomalies that might have been missed in first trimester should solely NIPT be performed as first-tier test, and the rate of adverse pregnancy outcome if NT normalizes before 14 weeks. METHODS: We performed a retrospective cohort study that included all pregnancies between January 1, 2007 and June 1, 2020 in Amsterdam UMC locations AMC and VUmc. We included fetuses with a crown-rump length (CRL) < 45 mm (∼11 weeks) and a nuchal translucency (NT) measurement ≥2.5 mm. Fetuses referred with an early increased NT and a major fetal anomaly at the dating scan were excluded, as were cases of parents with a family history of monogenetic disease(s) or recognized carriers of a balanced translocation. RESULTS: We included 120 fetuses of which 66.7% (80/120) had an adverse pregnancy outcome. Congenital anomalies were present in 56.7% (68/120), 45.8% (55/120) had a chromosomal anomaly. The prevalence of congenital anomalies was 30.3% in fetuses with NT 2.5-3.4 mm compared to 66.7% with NT ≥ 3.5 mm (p < 0.001). 16.7% (20/120) had a chromosomal anomaly that might have been missed by conventional NIPT in first trimester. We found an adverse pregnancy outcome of 24% in the group with a normalized NT compared to 78.1% in the group with a persistently increased NT (p < 0.001). CONCLUSION: An early increased NT should make the sonographer alert. In this selected cohort, an early increased NT was associated with a high probability of having an adverse pregnancy outcome. Regardless of CRL, we deem that an early increased NT ≥ 3.5 mm warrants referral to a Fetal Medicine Unit for an extensive work-up. NT normalization seems favorable, but a prospective study should define the appropriate work-up for NT in the lower range (2.5-3.4 mm).

Machine learning improves early prediction of small-for-gestational-age births and reveals nuchal fold thickness as unexpected predictor.

OBJECTIVE: To investigate the performance of the machine learning (ML) model in predicting small-for-gestational-age (SGA) at birth, using second-trimester data. METHODS: Retrospective data of 347 patients, consisting of maternal demographics and ultrasound parameters collected between the 20th and 25th gestational weeks, were studied. ML models were applied to different combinations of the parameters to predict SGA and severe SGA at birth (defined as 10th and third centile birth weight). RESULTS: Using second-trimester measurements, ML models achieved an accuracy of 70% and 73% in predicting SGA and severe SGA whereas clinical guidelines had accuracies of 64% and 48%. Uterine PI (Ut PI) was found to be an important predictor, corroborating with existing literature, but surprisingly, so was nuchal fold thickness (NF). Logistic regression showed that Ut PI and NF were significant predictors and statistical comparisons showed that these parameters were significantly different in disease. Further, including NF was found to improve ML model performance, and vice versa. CONCLUSION: ML could potentially improve the prediction of SGA at birth from second-trimester measurements, and demonstrated reduced NF to be an important predictor. Early prediction of SGA allows closer clinical monitoring, which provides an opportunity to discover any underlying diseases associated with SGA.

Skin edema in first trimester fetuses.

PURPOSE: The aim of this study was to prove an association between generalized skin edema and nuchal translucency (NT) thickness and its predictive value for aneuploidy and structural anomalies. MATERIALS AND METHODS: In this retrospective study fetuses with and without skin edema in the first trimester with an NT above 2.2 mm were compared. Statistical significance was calculated with the Chi-square test (p < 0.05). RESULTS: 237 fetuses were included in this study (median NT of 3.0; IQR: 2.5 - 3.9 mm, median CRL 68.8; IQR: 58.9 - 74.9 mm). 17.3 % presented with skin edema. The rate of skin edema was 1.3 % in the group with an NT < 95th percentile, 2.7 % in the group with an NT between the 95th and 99th percentile, 17.5 % with an NT of 3.5 - 4.4 mm, 36.4 % with an NT of 4.5 - 5.4 mm, 54.5 % with an NT of 5.5 - 6.4 mm and 95.5 % with an NT above 6.5 mm. 19 % had chromosomal disorders. The rate of aneuploidy was 61.0 % (25/41) in the group with skin edema which was significantly higher than the rate of 10.2 % (20/196) in those without skin edema (p < 0.0001). 12 % had structural anomalies in euploid fetuses. The rate of anomalies was 43.8 % (7/16) in the group with skin edema and significantly higher compared to 9.1 % (16/176) in those without skin edema (p < 0.0005). CONCLUSION: Our data show a clear association between the thickness of NT and the rate of skin edema. Skin edema has a high predictive value for aneuploidy or structural malformations. Therefore, fetuses with skin edema should have early malformation scans in case of normal karyotype.