Results
Among women enrolled in the SCRN study, 384 stillbirth cases that had
chromosomal microarray and fetal structural malformation assessments
were included in the present analysis. Among 384 stillbirth cases, 58
(15.1%) had abnormal CNVs and 326 (84.9%) had normal CNVs. As
previously described,10 cases with abnormal CNVs were
older, Hispanic, and with any fetal structural malformations in
comparison to cases with normal CNVs. Similarly, cases with abnormal
CNVs were not different in their proportions from those with normal CNVs
in regard to other socio-economic factors, parity, fetal sex, maternal
chronic hypertension, preeclampsia, diabetes and gestational diabetes.
The most common organ system-specific fetal structural malformations
were cardiac defects, followed by craniofacial and skeletal defects, and
hydrops. The proportion of cases with fetal structural malformations
(any anomaly) was higher among those with abnormal CNVs compared with
those with normal CNVs (46.7% vs. 19.6%; p-value<0.001;Figure 1 and Table S1 ). We also found organ
system-specific associations with abnormal CNVs. For example, the
proportions of cases with cardiac, craniofacial and skeletal defects
that had abnormal CNVs were higher than those that had normal CNVs
(26.3% vs. 4.3%; p-value<0.001, 21.8% vs. 2.3%;
p-value<0.001, and 19.2% vs. 4.0%; p=0.005, respectively).
Hydrops, cystic hygroma and gastrointestinal defects were more common
when abnormal CNVs were present, but in relatively smaller proportions
(all p-values<0.05). Malformations categorized as ‘other
anomaly’, umbilical cord abnormalities, central nervous system, thorax
and genitourinary defects were not different in their proportions of
abnormal CNVs in comparison to those in the normal CNVs group. The
proportion of stillborn fetuses with normal CNVs that had any fetal
structural malformation was lower than the proportion of those with
normal CNVs and had no fetal structural malformation (70.3% vs 89.4%,
p-value<0.001; Table S2 ). A pathogenic deletion of
1q21.1 involving 46 genes, including a known CHD1L gene, and a
duplication of 21q22.13 involving 4 genes (SIM2 , CLDN14 ,CHAF1B , HLCS ) were associated with a skeletal and cardiac
defect, respectively (Table 1 ).