Interpretation
It has been indicated that the commonest indications of
routine amniocentesis (between
16-24 gestational weeks) in China were the increased risk at maternal
serum screening and advanced maternal age
(35 years at the expected time of
delivery) 17. However, late detected aberrant
ultrasound findings (or a combination of ultrasound findings with other
earlier indications) was the most frequent indication of late
amniocentesis and has accounted for 88.3% in our cohort.
Among the 67 cases, 13 cases with ultrasound findings show the same
results with CMA reports. For instance, a fetus presenting with cardiac
anomalies had a microdeletion of chr22q11.2 compatible with DiGeorge
syndrome18. In another case, a fetus with the absence
of cauda cerebelli was found to have a microdeletion on chr7p22.3p21.1
and chr8p23.3p23.2, which is associated with Dandy-Walker syndrome(type
II)19.
Compared to
routine
amniocentesis, the complication rate of
late amniocentesis within one
week and one month are 9.6%
(11/115) and 11.3% (13/115), respectively. The overall
complication rate was 9.0% (115/1272). As Daum and coworkers reported
that only 18 complications were identified among their 291 patients
undergoing late amniocentesis in Israel1, while the
complication rate reported by Liao
and coworkers was 1.9% (only two complications were found among 108
patients) after third-trimester amniocentesis20. Owing
to the sample size is much more abundant in our cohort, the complication
rates of our study are higher than theirs, but similar to that reported
by Gabbay et al. 21 and consistent with a recent
meta-analysis22. Although our complication rate is
higher than that of routine amniocentesis23, it is
reasonable to speculate that at least some of the complications are
unlikely to have a direct association with amniocentesis owing to 88.7%
(102/115) complications took place in fetuses with abnormal ultrasound
findings.
The main
predictor
of PTB in singletons was fetal malformations (24/26, 92.3%), mainly
CNS anomalies (4/24, 16.7%) and
FGR (4/24, 16.7%). The presence of fetal malformations obviously
increases the risk of both PTB and IUD, compared to others without fetal
malformations. And pregnancies with double puncture are more likely to
suffer from PTB after late amniocentesis.
This result may offer opportunities
for doctors to consider both the indication for late amniocentesis and
the risks of PTB comprehensively.
On the other hand, the rate of detection of chromosomal aberrations via
CMA and ES are 10.5% and 8.3% respectively, while 92.3% of pathogenic
CNVs failed to be detected by karyotyping, suggesting that both CMA and
ES achieve better diagnostic yield than traditional karyotyping does.
Thus, advanced gene diagnosis technologies have a positive role in late
amniocentesis. Not only in late amniocentesis but also in routine
amniocentesis, the detection rate of CMA and ES, is higher than
karyotyping
obviously3, 24.
In
our cohort, the diagnostic rate
reaches the highest (31%) when suspected prenatal diagnosis results
become the indication of amniocentesis, following by Combination of
ultrasound findings (23.1%). It is comparable with the diagnostic rate
of routine amniocentesis following
abnormal ultrasound findings24.
The vast majority of women (86.4%) finally decide to terminate the
pregnancies after receiving pathogenic genetic results. 24.4% of women
with normal genetic results still terminate the pregnancies owing to the
severe ultrasound findings.
A considerable disadvantage of
late
amniocentesis, especially late in pregnancy, was the identification of
uncertain results like VOUS, likely pathogenic and likely benign. 41.5%
fetuses with uncertain results were terminated. The reason of 85.2% of
them was fetal abnormalities, while the other four
were even without abnormal
sonographic findings, suggesting that the unclear genetic results might
have reinforced their decisions. Of note, except one patient was lost to
follow up and the other one was IUD, Three out of the five fetuses whose
one of the CMA and ES result showed pathogenic or likely pathogenic were
terminated no matter with or without abnormal ultrasound finding. For
instance, the couple was referred for genetic counseling during their
second pregnancy due to the NIPT result showed trisomy 21 high risk.
After amniocentesis, the CMA result showed trisomy 21, but no abnormal
finding could be identified through ultrasound. Then the couple chose to
have a WES test, and it showed normal afterward. The couple finally
terminated the pregnancy.
Worth mentioning, all of the women pay close attention to their genetic
test results, which made it reasonable to cogitate the importance and
necessity of genetic information even if ultrasound findings are
severely abnormal. Moreover,
genetic information is also important for future pregnancies without any
doubt. In order to increase the accuracy of diagnosis and save time, we
also support the idea of offering CMA and ES simultaneously while
indeterminate ultrasound findings were identified. However, the economic
problem should be taken into account.