Table 1 Prenatal ultrasound findings in 312 patients with a normal chromosomal microarray (or a normal karyotype for 19 patients).

From: When to test fetuses for RASopathies? Proposition from a systematic analysis of 352 multicenter cases and a postnatal cohort

Prenatal findings

Total number of patients (n = 312)

Prenatal positive group (n = 47)

Negative group (n = 265)

p valuea

Postnatal positive group (n = 25)

Increased NT

230/312 (74%)

29/47 (62%)

201/265 (76%)

0.02

1/25 (4%)

   NT > 3 < 3.5

21/230 (9%)

0/29 (0%)

21/201 (10%)

0.03

   NT ≥ 3.5 ≤ 6

144/230 (63%)

17/29 (59%)

127/201 (63%)

   NT > 6

60/230 (26%)

12/29 (41%)

48/201 (24%)

   Unknown

5/230 (2%)

0/29 (0%)

5/201 (2%)

  Increased NT without CH

86/312 (28%)

7/47 (15%)

79/265 (30%)

0.03

1/25 (4%)

   Isolated

50/230 (22%)

0/29 (0%)

50/201 (25%)

NA

1/25 (4%)

   In associationc

180/230 (78%)

29/29 (100%)

151/201 (75%)

0/25 (0%)

 Mean NT (mm)b

5.0 (0.7–14.9)

6.4 (s.d. 3.0)

4.8 (s.d. 1.9)

0.005

2.6 (1.0–4.1)

Cystic hygroma

182/312 (58%)

30/47 (64%)

152/265 (57%)

0.4

0/25 (0%)

  1st trimester CH

58/182 (32%)

4/30 (13%)

54/152 (36%)

0.02

  Persistentd CH

125/182 (68%)

26/30 (87%)

98/152 (64%)

  Isolatede

88/182 (48%)

4/30 (13%)

84/152 (55%)

<0.0001

NA

  In associationc

94/182 (52%)

26/30 (87%)

68/152 (45%)

  CH without ↑ NT

34/182 (19%)

9/30 (30%)

25/152 (16%)

0.1

0/25 (0%)

  CH with ↑ NT

148/182 (81%)

21/30 (70%)

127/152 (84%)

  NT > 3 < 3.5

17/148 (11%)

0/21 (0%)

17/127 (13%)

0.03

NA

  NT ≥ 3.5 ≤ 6

88/148 (60%)

10/21 (48%)

78/127 (61%)

  NT > 6

43/148 (29%)

11/21 (52%)

32/127 (25%)

Increased NF

67/312 (21%)

17/47 (36%)

50/265 (19%)

0.002

0/25 (0%)

  NF > 6

62/67 (93%)

14/17 (82%)

48/50 (96%)

0.1

  NF > 15

5/67 (7%)

3/17 (18%)

2/50 (4%)

  Mean NF (mm)b

6.9 (3.0–28.0)

9.6 (s.d. 4.9)

6.3 (s.d. 3.6)

0.004

NA

Lymphatic anomalies

34/312 (11%)

9/47 (19%)

25/265 (9%)

>0.05

0/25 (0%)

Hydrops

60/312 (19%)

20/47 (42%)

40/265 (15%)

<0.0001

1/25 (4%)

  1st trimester hydrops

14/60 (23%)

2/20 (10%)

12/40 (30%)

0.08

  Persistentd hydrops

46/60 (77%)

18/20 (90%)

28/40 (70%)

Thoracic effusions or ascites

54/312 (17%)

22/47 (47%)

32/265 (12%)

<0.0001

4/25 (16%)

Congenital heart disease

71/312 (23%)

18/47 (38%)

53/265 (20%)

0.002

3/25 (12%)

  Cardiac defect

64/312 (21%)

15/47 (32%)

49/265 (18%)

0.02

3/25 (12%)

  HCM

13/312 (4%)

9/47 (19%)

4/265 (2%)

0.007

1/25 (4%)

  HCM without CD

7/13 (54%)

3/9 (33%)

4/4 (100%)

NA

0/25 (0%)

  Combined HCM + CD

6/13 (46%)

6/9 (67%)

0/4 (0%)

1/25 (4%)

Other associated findingsc

 Polyhydramnios

36/312 (12%)

14/47 (30%)

22/265 (8%)

<0.0001

8/25 (32%)

 Renal anomalyf

46/312 (15%)

14/47 (30%)

32/265 (12%)

0.0002

5/25 (20%)

 Macrosomia

12/312 (4%)

6/47 (13%)

6/265 (2%)

0.001

2/25 (8%)

 Mild ventriculomegaly

13/312 (4%)

7/47 (15%)

6/265 (2%)

0.0001

0/25 (0%)

 Short long bones

17/312 (5%)

7/47 (15%)

10/265 (4%)

0.007

1/25 (4%)

General findings

 Only one US finding

61/312 (20%)

2/47 (4%)

59/265 (22%)

0.004

6/25 (24%)

 Two or more US findings

251/312 (80%)

45/47 (96%)

254/265 (78%)

7/25 (28%)

 No US finding

NA

NA

NA

–

12/25 (48%)

  1. Nota bene. Analyses were based on all prenatal findings observed throughout pregnancy, so that patients without longitudinal data were excluded.
  2. CD cardiac defect (pulmonary valve dysplasia or stenosis, septal defect, aortic anomalies, tetralogy of Fallot, etc.), CH cystic hygroma, HCM hypertrophic cardiomyopathy, NA not applicable, NF nuchal fold, NT nuchal translucency, US ultrasound.
  3. aChi-square statistic or Fisher’s exact test, as appropriate; α error = 0.05.
  4. bWilcoxon–Mann–Whitney test was used because our data did not follow a normal distribution (p values <0.0001 for Shapiro–Wilk and Andersen–Darling normality tests).
  5. cOnly suggestive US findings of RASopathies as described in the literature were considered as associated findings.
  6. dCystic hygroma or hydrops present at 2nd trimester ultrasound and more (>15 gestational weeks for CH and >14 weeks for hydrops).
  7. eWithout another US finding, except increased NT.
  8. fMostly hydronephrosis.
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