Clinical strategy study on prenatal screening and diagnostic model for Down syndrome.

Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged < 35 years who underwent only one screening for foetal Down syndrome (DS), the detection rate, false positive rate and positive predictive value of NIPS for foetuses with DS were superior to those of the other four serological screening methods. Although applying NIPS as first-line screening method yields the highest efficacy and benefits, it currently lacks cost-effectiveness when compared to serological screening and sequential NIPS screening strategies.

Improved contingent screening strategy increased trisomy 21 detection rate in the second trimester.

PURPOSE: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection. METHODS: This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted. RESULTS: Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free ß-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively. CONCLUSION: Utilizing threshold values of AFP, free ß-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies.

A new contingent screening strategy increased detection rate of trisomy 21 in the first trimester.

BACKGROUND: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. METHODS: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. RESULTS: When cut-off values of free beta subunit of human chorionic gonadotropin (free ß-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. CONCLUSIONS: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Performance of noninvasive prenatal screening in twin pregnancies: a retrospective study of 5469 twin pregnancies.

OBJECTIVES: To evaluate the performance of noninvasive prenatal screening (NIPS) for the fetal common aneuploidy screening in twin pregnancies. METHODS: The data of 5469 women with twin pregnancies were collected in this retrospective observational study between January 2017 and December 2018. Patients underwent NIPS as first-line screening or after standard serum screening for fetal aneuploidy. The performance of NIPS was examined, and a regression analysis was performed to investigate testing failure in cases of low fetal fraction. RESULTS: In this study, 2231 (40.8%) patients opted for NIPS as the primary prenatal screening test, and 3238 (59.2%) opted for serum screening, including 440 patients who opted for NIPS after serum screening. Among the 2671 pregnancies with available NIPS outcomes, 11 cases of aneuploidy were identified, seven of trisomy 21 and four of sex chromosome aneuploidy (SCA). The sensitivity and specificity for trisomy 21 were 100% (95% CI, 56.1-100.0%) and 100% (95% CI, 99.8-100.0%), respectively. The positive predictive value (PPV) for SCA was 40.0% (95% CI, 13.7-72.6%). No false negatives were found, with a negative predictive value (NPV) of 100% (95% CI, 99.8-100.0%) in total. In 32 pregnancies who failed NIPS test without available NIPS outcomes due to low fetal fraction, the regression analysis demonstrated that increasing BMI and assisted reproductive technology treatment were significant independent predictors. CONCLUSIONS: NIPS is a high-performing routine primary prenatal screening test in twin pregnancies, with a high PPV and low false positive rate for detecting trisomy 21. It is also useful to identify common sex chromosome aneuploidies in twin pregnancies, with similar performance to that reported in singleton pregnancy.

A Retrospective Analysis Of Different Contingent Screening Models For Fetal Down Syndrome In Southwestern China.

To discuss combinations of traditional screening and noninvasive prenatal screening (NIPS) and to compare which traditional screening is the most suitable first-line screening approach to NIPS, pregnant women were recruited in this retrospective observational study. Pregnant women underwent one of four traditional screening tests. The 9 contingent models were combined by high risk cut-offs of 1:50, 1:100, 1:270 and intermediate risk cut-offs of 1:1000, 1:1500, 1:2000. We analyzed cost and performance of various screening models with contingent screening of different risk cut-offs. Compared with other screening tests, combined first-trimester screening (CFTS) had the lowest proportion of high risk (≥1:270) with the highest detection rate (DR) (78.79%) and the lowest proportion of intermediate risk (1:271~1:1000). When intermediate risk was 1:51 ~1:1500, CFTS as first-line screening had the lowest cost with DR of 93.94%. Other screening tests as the first-line screening with intermediate risk of 1:51~1:1000 had the lowest cost, there DR were 90.91%, 84.62%, 91.67%, respectively. Our study demonstrated if only one traditional screening was allowed to screen pregnant women, CFTS was recommended as the first choice. According to local health and economic conditions, adopting appropriate traditional screening with suitable cut-offs as first-line screening will contributed to a cost-effective screening model.

[Analysis of 21 723 Pregnant Women's First Trimester Screening for Down Syndrome in Sichuan Province].

OBJECTIVE: To compare the effect of different first-trimester screening programmes for Down syndrome in Sichuan Province. METHODS: We retrospectively collected the data of singleton pregnancies that were screened by serum biochemistry markers combined with nuchal translucency screening tests in the first trimester in Prenatal Diagnosis Center of West China Second University Hospital of Sichuan University from January 2011 to December 2017. The fetal chromosome results were obtained by amniocentesis or by telephone follow-up. The screening effect of maternal age, nuchal translucency thickness, maternal serum biochemistry markers and combined screening in the first trimester were analyzed. RESULTS: Among the 21 723 singleton pregnancies, 33 cases were diagnosed as Down syndrome, and 19 cases were diagnosed as trisomy 18 sex chromosome abnormalities were found in 4 cases, and other chromosome abnormalities were found in 8 cases. For the combined screening, the detection rate of Down syndrome was 72.73%, and the false positive rate was 2.49%; the detection rate of trisomy 18 syndrome was 73.68% with the false positive rate of 0.39%. With a 5% false positive rate, maternal age, nuchal translucency thickness, serum biochemistry markers and combined screening would respectively detect 15.15%, 57.58%, 60.61% and 87.88% of Down syndrome fetuses. CONCLUSION: Compared with the other three screening programmes, the combined screening can effectively screen fetuses with Down syndrome and other chromosomal abnormalities.

[Correlation analysis between serum free testosterone and total testosterone in Chengdu females].

This paper is aimed to analyze the correlation between serum free testosterone (FT) and total testosterone (TT) to acquire a cutoff about using total testosterone to diagnose hyperandrogenism in Chengdu females. We investigated 1854 women by cluster sampling method, detected their serum FT levels and TT levels, scored relative items, analyzed the correlation and made the ROC curve to get a cutoff of TT levels. Serum FT had a linear correlation with serum TT (r = 0.597, r2 = 0.356, P < 0.001). The cutoff value was 0.635 ng/mL. The specificity and sensitivity were 76.3% and 77.24%, respectively. No correlation found between serum FT and Ferriman-Gallway Score (P = 0.392). Positive correlations were seen between serum FT and Plewig-Kligman Score (r = 0.137, P < 0.001), serum TT and Ferriman-Gallway Score (r = 0.069, P = 0.003) and serum TT and Plewig-Kligman Score (r = 0.092, P < 0.001). There is a linear correlation between serum FT and TT. We can diagnose hyperandrogenism according to the serum TT cutoff value (0.635 ng/mL). Its clinical symptoms are not paralleled with the biochemical test results.

[Effects of eight environmental endocrine disruptors on insulin resistance in patients with polycystic ovary syndrome: a preliminary investigation].

OBJECTIVE: To investigate the relationship between 8 endocrine-disrupting chemicals in the serum and insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: This study was conducted among 60 patients with PCOS, including 23 with insulin resistance (PCOS-IR) and 37 without insulin resistance (PCOS-NIR), and 29 non-PCOS women seeking medical attention for infertility or menstrual disorder (control group). The serum levels of 6 phthalic acid esters (PEAs), bisphenol A (BPA) and octylphenol (OP) were measured in all the subjects. RESULTS: The levels of PAEs, BPA and OP showed no significant differences between PCOS patients and the control group (P>0.05). The serum level of OP was significantly lower in patients PCOS-IR than in those with PCOS-NIR (47.89 ng/ml vs 60.24 ng/ml, P<0.05). CONCLUSION: PEAs and BPA do not produce obvious effect on the pathogenesis of PCOS or contribute to insulin resistance, but OP may play a role in insulin resistance in PCOS patients.

[On the relationship between serum total adiponectin and insulin resistance in polycystic ovary syndrome].

It is the intent of this investigation to gain an insight into the relationship of serum total adiponectin with polycystic ovary syndrome (PCOS) and insulin resistance. Fifty-eight PCOS patients were enrolled (29 with high serum insulin level and 29 without), at the same time, 29 non-PCOS women with normal weight were included as control. The influencing factors of total adiponectin, PCOS and insulin resistance were analyzed. The serum total adiponectin of PCOS patients and all participants were found to be negatively related to waist hip ratio (r = -0.39, r = -0.36) and InHOMA-IR (r = -0.53, r = -0.45), respectively. Adiponectin was not a protective factor of PCOS (P > 0.1), but it was that of PCOS-insulin resistance (OR = 0.81; 95% CI: 0.67-0.97; P = 0.02). LH/FSH (OR = 1.51; 95% CI: 1.16-1.96; P = 0.01) and InHOMA-IR (OR = 1.26; 95% CI: 1.10-1.44; P = 0.01) were risk factors of PCOS, and waist hip ratio was that of PCOS-insulin resistance (OR = 8.57; 95% CI, 2.14-34.30, P = 0.01). Adiponectin might influence fasting insulin and InHOMA-IR (B = -0.22, P = 0.001; B = -0.02, P = 0.002). These data signify that adiponectin is not directly related with PCOS, but it is related with PCOS-HL Adiponectin might participate in the pathophysiologic mechanism of PCOS by influencing insulin sensitivity.

[Impact of controlled ovarian hyperstimulation delayed, which occurs after functionally pituitary downregulation by depot GnRH agonist, on the outcome of in vitro fertilization and embryo transfer].

OBJECTIVE: This study observed the influence on hormone, embryos and clinical outcomes when the starting time of controlled ovarian hyperstimulation (COH) was delayed after applying a half-dose depot gonadotropin-releasing hormone agonist (GnRHa). METHODS: A total 207 cycles were divided into 3 groups: control group (98 cycles, which performed daily low dose GnRHa during the mid-luteal phase in patients' menstrual cycles and reduced the dosage to a half at the next day 3, and added gonadotropin (Gn), conventional group (63 cycles, in which pituitary desensitization was obtained with a half-dose depot GnRHa in the mid-luteal phase, and then Gn was added at day 3) and delayed group (46 cycles, having the same usage of GnRHa to conventional group, but not adding Gn until day 7). RESULTS: The cancellation rate of cycle in conventional group was the highest (P < 0.01). At the beginning of COH, serum E2 and LH levels in delayed and control group were significantly higher than those in conventional group (P < 0.01). On the day of HCG given, serum E2 level in control group was the highest (P < 0.05). LH level in delayed and control group was higher than that in conventional group (P < 0.01). Concerning the clinical efficacy and outcome, the numbers of Gn ampoules and periods for stimulation were less in delayed group than in conventional group; the numbers of retrieved and fertilized oocytes, numbers of good quality embryos, clinical pregnancy rate and embryo implantation rate in delayed and control groups were significantly more than those in conventional group (P < 0.01). In ICSI cycles, the numbers of retrieved oocytes and metaphase II oocytes in delayed and control group were more than those in conventional group. CONCLUSIONS: A half-dose depot GnRHa may produce over suppression to pituitary gland in fertilization in vitro, appropriate delay of COH starting time can decrease ovarian stimulation period and ampoules of Gn, and increase retrieved good quality oocytes, so we could achieve a larger number of good quality embryos with a good chance of implantation.

[The relationship between leptin, insulin-like growth factor-1 (IGF-1) and hyperinsulinemia of patients with polycystic ovarian syndrome].

OBJECTIVE: To identify the effect of IGF-1 and leptin on the hyperinsulinemia (HI) of patients with polycystic ovarian syndrome (PCOS). METHODS: The case-control compared method was applied to the study. Ninety-two PCOS and 92 control subjects were involved in the study. The group of PCOS was further divided into two subgroups of 46 PCOS-HI and 46 PCOS-NHI. The leptin, IGF-1 and other hormones such as serum testosterone, DHT, DHEA, DHEA-S were measured by RIA method. RESULTS: Leptin and IGF-1 were higher in PCOS group (16.8 +/- 9.8 ng/mL, 214.8 +/- 131.6 ng/mL) than those in control group (11.6 +/- 6.8 ng/ mL, 118.0 +/- 82.9 ng/mL respectively, P < 0.05). Serum leptin level was higher in hyperinsulinemia group (9.2 +/- 10.2 ng/mL) than that in normal insulin group (12.5 +/- 7.6 ng/mL, P < 0.05). IGF-1 (208.7 +/- 109.7 ng/mL vs. 151.7 +/- 120.0 ng/mL, P = 0.66) and fasting glucose (5.1 +/- 0.5 mmol/L vs. 4.9 +/- 0.4 mmol/L, P = 0.15) had no significant difference between two groups. Multiple logistic regression showed that after the body mass index (BMI) adjusted, the testosterone, LH/FSH, DHT, DHEA, and DHEA-S, leptin and IGF-1 showed to be the independent risk factor for PCOS, but not to be for hyperinsulinemia in patients with PCOS. CONCLUSION: The leptin and IGF-1 may contribute to the pathogenesis of PCOS, but the relationship between leptin, IGF-1 and hyperinsulinemia needs more researches to confirm.