RESULTS
During the study period, 10,478 pre-NIPT were performed at any
gestational age and 104 cases of reported fetal oedema with a CRL
between 28 mm and 44 mm were identified. Nuchal oedema was present in 40
(38.5%) and generalised oedema in 64 (61.5%) cases. Fetal hydrops was
present in six of the generalised oedema cases (9.4%).
The characteristics of the study population and pre-NIPT ultrasound are
shown in Table 1. The median maternal age was 33.6 years (interquartile
range (IQR) 30.3-37.6) and there were no significant differences in the
maternal characteristics, gestational age, oedema thickness measurement,
nuchal translucency at 11 to 13+6 weeks or cell-free
DNA test results between the subgroups of fetal oedema.
The agreement between the two operators in subclassifying the cases into
nuchal oedema, generalised subcutaneous oedema or fetal hydrops was high
(ICC 0.91, 95%CI 0.87 – 0.94, p<0.001).
Pregnancy outcomes were available in 93 (89.4%) cases. Overall, in
seven cases cell-free fetal DNA testing yielded high-risk results, and
they were all true positive findings (Table 2). Relevant chromosomal
anomalies were identified in 21.5% (20/93), occurring in 12.1% (4/33)
of the nuchal oedema and 26.7% (16/60) of the generalised oedema or
hydrops cases. Of the six cases of fetal hydrops, three (50%) were
affected by trisomy 18 and three resulted in a phenotypically normal
infant at birth after low risk cfDNA testing and normal NT at 11 to
13+6 weeks.
Other structural anomalies with normal karyotype were identified in
another four (4.3%) cases. Seventy-one infants (76.3%) were liveborn
(66 with normal ultrasound follow up examinations and phenotypically
normal infants at birth, one with monosomy X, two with major fetal
anomalies and normal chromosomal microarray, and two with variants of
unknown significance on the chromosomal microarray). Miscarriage
occurred in four cases (4.3%), of which three had confirmed aneuploidy
on products of conception, and termination of pregnancy was performed in
18 cases (19.4%, 16 with chromosomal abnormalities and two with normal
karyotype but major structural anomalies at 11 to 13+6weeks, Table 2).
There was a significant association of the oedema thickness at early
gestational age and increased nuchal translucency at 11 to
13+6 weeks (p<0.001,
R2=0.187, Figure 1). Nevertheless, the oedema resolved
(NT below 3.5 mm) by 11 to 13+6 weeks in 81.9% of the
cases, and these cases had a significantly lower adverse outcome rate
than those with NT ≥ 3.5 mm (10.9% versus 76.5%, p<0.001).