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).