Demographic data and general characteristics
During this period, a total of 13,690 singleton pregnancies ( ranging from 16 weeks + 0 days to 38 weeks + 5 days ) were recruited in the study, including 10,830 non-AMA women with the average age of ( 27.1 ± 4.15 ) year old and 2,860 AMA women with the average age of ( 38.3 ± 3.48 ) year old. Among these, ARSA was prenatally detected with the overall incidence of 0.69 % ( 95 / 13,690 ), including 63 cases ( 63 / 95, 66.32 % ) with isolated ARSA. In non-AMA group, 70 of 10,830 fetuses were prenatally visualized with an ARSA, with the incidence of 0.65%. And in AMA group, 25 out of 2,860 fetuses were visualized with an ARSA, with the incidence of 0.87%. In our study, chromosomal abnormalities were detected with a rate of 0.75 % ( 102 / 13,690 ), including 0.63 % ( 65 / 10,380 ) in non-AMA group and 1.29 % ( 37 / 2,860 ) in AMA group. Demographic data and general characteristics were listed in Table 1.
Of the isolated ARSA fetuses, 63 ( 66.32 % ) cases were born including 15 ( 60.00 % ) cases in AMA group and 48 ( 68.57 % ) cases in non-AMA group. Only one of the simple ARSA case in AMA group were detected with sex chromosome aneuploidies ( SNP Array arr (1-22)x2,(X)x1-2 ), and no obvious abnormality was found in the rest during the clinical follow-up observation. The woman had no pregnancy high-risk factors and complications with thecritical risk of Down's syndrome screen. Sex chromosome aneuploidies was firstly implied by Cell-free DNA detecting and verified by amniocentesis karyotype analysis. This case of isolated ARSA can only be a random coincidence, which was excluded in statistical analysis.
Of the 32 cases of ARSA with additional structural malformation, 28 cases had their pregnancies terminated and 11 cases of them had abnormal karyotype. There were 4 patients in AMA group and 7 patients in non-AMA group, including trisomy 13 syndrome, trisomy 18 syndrome and trisomy 21 syndrome. The other four normal karyotype fetuses were delivered smoothly, respectively associated with a choroid plexus cyst, unilateral renal agenesis, persistent left superior vena cava and pulmonary sequestration.
Incidence rate of chromosomal abnormalities
In the ARSA positive group, the incidence rate of chromosomal abnormalities was 20.00 % ( 5 / 25 ) in AMA group and 10.00 % ( 7 / 70 ) in non-AMA group. Furthermore, follow-up on fetus with combined ARSA and chromosomal abnormalities, we found 58.33 % ( 7 / 12 ) cases with trisomy 21 syndrome, 25.00 % ( 3 / 12 ) cases with trisomy 18 syndrome, 8.33 % ( 1 / 12 ) cases with trisomy 13 syndrome and 8.33 % ( 1 / 12 ) cases with chimeric Turner syndrome ( 45X / 46XX ). Among these combined ARSA, the incidence of chromosomal abnormalities was 34.38 % ( 11 / 32 ) and the incidence of trisomy 21 syndrome was 21.88 % ( 7 / 32 ) including 30.00 % ( 3 / 10 ) in AMA group and 18.18 % ( 4 / 22 ) in non-AMA group respectively. More information was detailed in Tables 2.
The incidence rate of chromosomal abnormalities in AMA group was much higher when comparing to that in non-AMA group ( = 13.79, df = 1, P < 0.001, OR = 0.46, 95% CI : 0.31 - 0.69 ). While there was no difference in ARSA incidence rate between AMA and non-AMA group ( = 1.39, df = 1, P = 0.24, OR = 1.36, 95% CI : 0.856 - 2.14 ), and so was that in isolated and combined ARSA ( = 0.17, df = 1, P = 0.68, OR = 1.18, 95% CI : 0.66 - 2.12 and = 1.50, df = 1, P = 0.22, OR = 1.7, 95% CI : 0.82 – 3.65 ). The risk of chromosomal abnormalities significantly increased with ARSA detected ( = 182.77, df = 1, P ﹤ 0.001, OR = 21.70, 95% CI : 11.44 – 41.14 ). Among AMA and non-AMA ARSA positive cases, the incidence increased to 20.00 % ( = 69.11, df = 1, P ﹤ 0.001 , OR = 21.90, 95% CI : 7.74 – 61.96 ) and 10.00 % ( = 104.35, df = 1, P ﹤ 0.001, OR = 20.50, 95% CI : 9.008 – 46.66 ) respectively. The Odds Ratio for AMA and non-AMA was homogeneity ( = 0.01, P =0.92 ). Thus, age was not a confounding factor in the association between ARSA and aneuploidy. The Mantel-Haenszel Common Odds Ratio estimated was 21.06, 95% CI : 11.05 – 40.15, P < 0.001. Similarly, with additional ultrasonic findings, chromosomal abnormalities risk increased, simultaneously in AMA group and non-AMA group ( Fisher’s exact test, all P < 0.001 ).
The likelihood ratio and predictive value of ARSA for chromosomal abnormalities were gathered in Table 3. İn AMA group, the likelihood ratio of combined ARSA for chromosomal abnormalities was 246.00, which was higher than that in entire cohort and non-AMA group ( respectively 69.76 and 97.82, all P < 0.001 ).