The commonest indications of routine amniocentesis (16–24 gestational weeks) in China is advanced maternal age and the increased risk of serum screening(14). However, late detected fetal abnormalities (or a combination of fetal abnormalities with other indications) are the most common indication of late amniocentesis. It has accounted for 86.2% in our cohort, consistent with a recent study(9), the central nervous system abnormalities (16.3%, 184/1130) was the most common ones.
Our sample size is larger than the other studies. And the overall complication rate after the procedure is 7.8%, and is higher than that reported by Daum et al. (6.2%)(1), Liao et al. (1.9%)(15) and Geffen et al. (6.6%)(11), but it’s in accordance with the 8% complication rate reported by Gabbay et al.(16) and consistent with a recent meta-analysis(17). Although our complication rate is higher than the second trimester amniocentesis(11), it is reasonable to speculate that at least some of the complications are unlikely to have a direct association with amniocentesis because 86.3% (88/102) complications took place in fetuses with abnormalities. In this study, complication rate within the first week was 0.7% and within one month was 1.5%, respectively.
We did not analyze all kinds of complications but focused on PTB and IUD which were the most common ones. PTB occurred in 33 women (2.6%) after amniocentesis, of which four had pathogenic chromosomal disorders, whereas four of sixteen women suffered from IUD (1.2%) had pathogenic chromosomal disorders. In our cohort, PTBs were associated with fetal malformations (24/25, 96%), mainly CNS anomalies (4/25, 16%) and FGR (4/25, 16%). PTB occurred in 0.7% (9/1243) in singleton pregnancies, while it occurred in 5.9% in twin pregnancies within one-month post-procedure. As for IUD, only two of the 16 IUD cases reported no fetal malformations. And IUD occurred in 0.2% in singleton pregnancies, while it occurred in 11.8% in twin pregnancies.
The presence of fetal malformations and pathogenic chromosomal disorders obviously increases the risk of both PTB and IUD, compared to others without these risk factors. In addition, twin pregnancies are more likely to be high-risk for PTB and IUD after late amniocentesis. This result may provide clinicians information to balance both the indication for late amniocentesis and the risks.
The total yield of abnormal genetic results was 10.2% which was higher than a recent study by Geffen et al.(11) and Daum et al.(1) with similar indications. As a referral center, a significant number of our patients are referred due to guarded prognosis. However, 86.4% of pathogenic CNVs failed to be detected by karyotyping, demonstrated that both CMA and WES achieve better diagnostic yield than traditional karyotyping as that in the second trimester amniocentesis(3, 18). In our cohort, the diagnostic rate reaches the highest (35.7%) when abnormal NIPT results become the indication of amniocentesis, following by multiple abnormalities (23.8%). It is comparable with the diagnostic rate of second trimester amniocentesis for fetal structural abnormality(18). The vast majority of women (88.7%) decided to terminate the pregnancies after receiving pathogenic genetic results. Twenty-nine percentage of women with normal genetic results still opted for termination of pregnancies due to the severe ultrasound findings.
In China, termination of pregnancies after 24 gestational weeks is legal in cases with major fetal abnormalities. Therefore, late amniocentesis can provide more information for patients to decide whether to continue the pregnancy. Even in places where late termination is not allowed, performing late amniocentesis and exploring the etiology remains useful. It can provide patients opportunities to begin to anticipate lifestyle changes and apply for assistance from relevant supporting groups and resources.
A considerable disadvantage of late amniocentesis, especially late in pregnancy, is the identification of uncertain results like VUS, likely pathogenic and likely benign. Forty-seven percentage of fetuses with uncertain results were terminated. The reason for this is that 88.7% of them are with fetal abnormalities, while the other 12.3% are fetuses with abnormal NIPT results. Except one patient is lost and the other one died, half of the eight fetuses with pathogenic or likely pathogenic results are terminated regardless of the abnormal ultrasound finding.
Pregnant women paid close attention to their genetic test results, which made it reasonable to consider the importance and necessity of genetic information even if ultrasound findings are severely abnormal. Moreover, genetic information also plays an important role in future pregnancies. To increase the accuracy of diagnosis and save time, we also recommend offering CMA and WES simultaneously when sonographic abnormalities were identified. However, the cost-effectiveness should be assessed.
Strengths and limitations
Our study has some limitations. There were 75 women who were lost of follow-up. Our study started from 2014. However, WES was underdeveloped and unavailable at that time. So all our cases of WES were collected in the last two years. Furthermore, we did not analyze all kinds of complications but only focused on PTB and IUD, which were most common. The assessment of complications and diagnostic yield could be inadequate.
This study also has several strengths. Although previous studies (1, 11, 15) have reported some data of late amniocentesis, a large clinical investigation is lacking. The sample size of our cohort is larger than the previous ones, so that our data could be more persuasive. Our study provided information of late amniocentesis which can improve the prenatal diagnosis and postnatal care for women.