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First trimester screening protocol using combined test. NT, nuchal thickness; PAPP-A, pregnancy-associated plasma protein-A; fβhCG , free β-human chorionic gonadotrophin.
Source publication
Objective
This study was designed to review the screening performance of combined test at the Ewha Womans University Mokdong hospital.
Methods
All women admitted for routine antenatal care between January 1st 2008 and December 31st 2012 with a known pregnancy outcome were included in this study, totaling 1,156 women with singleton pregnancies pres...
Context in source publication
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Objective
Early diagnosis and treatment are critical to minimize the complications of gestational diabetes mellitus (GDM). Therefore, the present study aimed to determine whether first-trimester screening test biochemical markers could be an early predictive model for GDM.
Material and Method
This retrospective study was performed by accessing the...
Background:
The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use.
Methods:
A routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were...
Objective
To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers.
Methods
This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadot...
Objectives
This study aimed to evaluate the effect size of each parameter used in the first trimester Down Syndrome (DS) risk analyses by using multiple regression analysis techniques.
Methods
This data mining study included data of 44,260 pregnant women screened at the Acibadem Labmed laboratories from 2010 to 2019. In this study, risk was calcul...
Citations
... Since the incorporation of nuchal translucency (NT) in first-trimester ultrasound screening (FTS) for Down's syndrome [1], it has become an indispensable tool for screening for fetal aneuploidy in conjunction with maternal serology [2][3][4]. Although cell-free DNA testing has minimized the role of NT in first-trimester aneuploidy detection, the advancement of ultrasound technology and knowledge of fetal anatomy has enabled early pregnancy screening for fetal structural abnormalities. ...
Background: To explore the effectiveness of standardized first-trimester ultrasound screening (FTS) in detecting fetal structural abnormalities in a non-selective population. Methods: A retrospective study was performed on 7523 fetuses (6376 single and 569 twin pregnancies) who underwent FTS between 11 and 13+6 weeks’ gestation. All fetuses received anatomy scans using a standardized protocol. Results: 147 fetuses (133 single and 7 twin pregnancies) were lost to follow up. Of the remaining 7376 fetuses, 119 (1.61%, 119/7376) developed structural malformations, with 64 cases (53.8%, 64/119) identified during the first trimester. The remaining cases were detected during the second trimester (24.4%, 29/119), the third trimester (1.68%, 2/119), and postnatally (20.2%, 24/119). There were 4 cases of suspected ventricular septal defect (VSD) by FTS, which were later confirmed to be normal. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for FTS were 54.2%, 99.9%, 94.1%, and 99.3%, respectively. Forty eight fetuses, accounting for 10.6% of the total (452), with thickened nuchal translucency (NT) (above the 95th percentile) showed structural malformations. This was significantly higher than the prevalence of structural abnormalities found in fetuses with normal NT (1.0%, 71/6924) (p < 0.01). Conclusions: Standardized FTS is highly effective in detecting fetal structural malformations early, with impressive specificity, PPV, and NPV. Increased NT suggests detailed anatomy screening and helps guide treatment. However, while standardized FTS is an invaluable tool, it cannot fully replace the sensitivity of second- and third-trimester ultrasound screening. Clinical Trial Registration: The study was registered at https://www.chictr.org.cn (registration number ChiCTR-SOC-17010976).
... In 2015, 73.6% of pregnant women who underwent combined first trimester screening in California were younger than 35 20 . The results from Korea were almost identical, as 78.4% of pregnant women were younger than 35, with 49% being aged from 30 to 35 21 . The combined first trimester screening at the Split University Hospital Center is performed between the 10 th week and the end of the 14 th week of pregnancy, in accordance with the international standards and evidence-based medical recommendations 5,8 . ...
... In developed countries, 50% to 80% of pregnant women opt for early amniocentesis or some other confirmatory method after a high-risk combined first trimester screening result [18][19][20][21] . The acceptance rate of early amniocentesis in the Split University Hospital Center was lower than the above and amounted to 40%. ...
... Despite the establishment of NTT measurement as a tool for screening fetal chromosomal aberrations, its popularity and application vary within different societies (Park et al., 2016). In our society, however, there is an obvious paucity of its application. ...
Background: Nuchal Translucency Thickness (NTT) is a hypo-echoic region of subcutaneous fluid accumulation in the posterior neck region at the level of the cervical spine between the skin and soft tissues and is mostly found at 11–13 weeks of fetal gestation. It is visualised with a mid-sagittal ultrasound view of the fetus in a neutral position. The NTT provides a risk assessment for chromosomal abnormalities which has been used as a marker of possible fetal abnormalities. Hence, the justification to conduct the present study. Aim: To establish the mean fetal nuchal translucency thickness with corresponding gestational age (GA) and to assess the correlation between Crown Rump Length (CRL), GA, and NTT among apparently healthy pregnant women. Methods: A cross-sectional study was conducted among 150 apparently normal consenting pregnant women in their late first trimester in the Radiology department of Muhammad Abdullahi Wase Teaching Hospital, Kano from February 2021 to May 2021. Ultrasonographic measurements of the crown-rump length (CRL), gestational age (GA), and NTT were performed on pregnancies within 11 to 13 weeks of gestation. Their 2.5th, 25th, median and 97.5th percentiles of the NTT, GA, and CRL were determined using SPSS version 23 (IBM, 2017). Indicate correlation… as part of the analysis. Results: Median NTT at 11-13+6 weeks of gestation was found as 3.0±0.10mm. The NT thickness increased with increasing CRL and gestational week in the first trimester. The correlation coefficient between NTT and CRL as well as GA were 0.472 and 0.451, respectively. Conclusion: The overall mean NTT in Kano fetuses was determined. These should be useful for first-trimester screening in ruling out potential fetal chromosomal abnormalities in Kano, Nigeria.
... GA estimation is also important in the evaluation of intrauterine growth restriction (IUGR) and in the interpretation of biochemical tests (such as human chorionic gonadotropin and alpha-fetoprotein) for prediction of risks of congenital anomalies and pathological foetal development. [1] Furthermore, accurate knowledge of GA also determines the modality of intervention when a foetal anomaly is detected. Almost all clinical decisions in pregnancy management require an accurate knowledge of GA. ...
Purpose:
The aim of this article is to evaluate the accuracy of placental thickness (PT) in determination of gestational age (GA) in normal singleton foetuses.
Materials and methods:
The study was a cross-sectional descriptive study which recruited consecutively a total of 406 pregnant women with singleton pregnancies (at 15-40 weeks of gestation), referred for routine obstetric ultrasound (US) scan at the National Hospital, Abuja from October to December 2019. Biparietal diameter (BPD), femur length (FL), head circumference (HC), abdominal circumference (AC), and PT were measured using standard protocols. All measurements were calculated by taking three best measurements, and the mean of the measurements was taken and recorded for each participant. Pearson's correlation analysis was computed to determine linear relationships between variables. A significant statistical level was determined at a critical value of P < 0.05.
Results:
The mean age was 31.8 ± 4.8 years. The mean PTs in the second and third trimesters were 23.2 ± 3.1 and 34.1 ± 3.7 mm, respectively. PT had a linear relationship and a statistically significant positive correlation (r=0.99, P = 0.00) with GA. There was also a statistically significant positive correlation between PT on the one hand, and BPD, AC, HC, FL, PT, and GA, on the other hand.
Conclusion:
There was a significant and strong positive correlation between PT and GA. The study shows that US measurement of PT is a reliable method of estimating GA in singleton pregnancies in Nigeria.
... Maternal age at the first prenatal visit with a diagnosis of first trimester check-up record was summarised using mean and SD and compared between the NIPT and no-NIPT groups using Student t-test. Categorical variables including type of health plan, grouped age (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and 45+), and specific risk factors including insufficient prenatal care, social problems, genitourinary infection, gestational diabetes, grand multiparity, hypothyroidism, substance/alcohol abuse, overweight/obese and hypertension in pregnant women were compared between the NIPT and no-NIPT groups and were summarised using frequency and percentage. Type of health plan was regrouped into two, commercial insurance versus all the others to address the small number of patients in each non-commercially insured or uninsured subgroups. ...
... 37 38 In combination with invasive diagnostic testing, the standard screening process without NIPT already achieved 100% sensitivity and negative predictive value. 39 This likely ...
Objective
Non-invasive prenatal testing (NIPT) is a front-line screening for fatal chromosomal aneuploidy. In pregnant women with a risk of having fetal congenital disorders, NIPT is anticipated to reduce the needs of invasive prenatal diagnostic test (IPD). The objective of this study was to understand the acceptance of NIPT and the utility of NIPT to mitigate concerns about IPD in the US high-risk pregnancy management.
Design and setting
This was a retrospective observational research using healthcare records obtained from an academic healthcare system in the US. The study consisted of site-level longitudinal analysis and patient-level cross-sectional analysis.
Participant
A total of 5660 new high-risk pregnancies with age ≥35 years were identified for the longitudinal trend analysis. Cross-sectional utility assessment included 2057 pregnant women.
Exposure and outcome measures
Longitudinal trends of NIPT order, IPD procedure and the number of patients diagnosed with high-risk pregnancy were descriptively summarised. In the cross-sectional assessment, we tested the association between the use of NIPT and IPD using multivariable regression.
Results
The rate of increase in the NIPT use exceeded the changes in the number of high-risk pregnancies with age ≥35 years, while the number of annual IPD procedures has fluctuated without specific trends. There was no significant association between the numbers of NIPT and IPD with the adjusted ORs between 0.90 and 1.14 (p>0.1). The order of NIPT was not selected as an independent variable predicting the use of IPD. Clinical characteristics indicating low socioeconomic status and limited healthcare coverage are associated with less use of NIPT and lower clinical utility.
Conclusion
Although prenatal care accepted NIPT over the last decade, the utility of NIPT in mitigating concerns on IPD is unclear and needs further investigation. Limited clinical utility should be addressed in the context of disparity in prenatal care.
... In a normal pregnancy, the concentration of PAPP-A increases exponentially, while the concentration of β-hCG, after the initial increase, decreases between 10 and 14 weeks of pregnancy [5]. A PAPP-A MoM decrease below 0.500 on average, along with β-hCG MoM decrease below 0.300 in maternal serum is considered to characterize trisomy 18 [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
... Non-invasive, first-trimester prenatal screening encompassing a combination of maternal serum biochemistry assays (β-hCG and PAPP-A) and ultrasound-assessed NT enables accurate identification of approximately 90% of chromosomal abnormalities with 5% false positive results [5,6,8,9,20]. The components of the first trimester testing do not always correlate with each other in accordance with [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
... Non-invasive, first-trimester prenatal screening encompassing a combination of maternal serum biochemistry assays (β-hCG and PAPP-A) and ultrasound-assessed NT enables accurate identification of approximately 90% of chromosomal abnormalities with 5% false positive results [5,6,8,9,20]. The components of the first trimester testing do not always correlate with each other in accordance with [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
Objective:
The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing.
Material and methods:
Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of β-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18.
Results:
PAPP-A and β-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and β-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and β-hCG MoM 0.2-0.5 range.
Conclusions:
Maternal free β-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal β-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and β-hCG MoMs, fetal NT measurement was an requirment.
... In Turkey, all pregnant women should be offered one of the antenatal screening tests according to the guideline of the Ministry of Health [2] . Combined test (CT) and triple test (TT) are the most widely used screening approach for women who are under 35 years-of-age [3][4][5] . Women who are detected for high-risk ( ≥ 1/250) should undergo invasive tests including amniocentesis (AC), chorionic villus sampling, or cordocentesis for definitive diagnosis. ...
Objectives
To provide information to the government about the budget impact of implementing non-invasive prenatal testing (NIPT) into prenatal screening strategies to detect Down syndrome (DS) in singleton pregnancies in Turkey; the likely costs or savings associated with NIPT in comparison to the current practice were calculated.
Methods
A decision-analytic model was developed to calculate the cost estimates for 1,309,771 women who gave birth in 2016; 84.8% of whom were <35-years-of-age. The superior combined test (CT) among current strategies is compared with contingent NIPT for women < 35-years-of-age; and usual practice of amniocentesis (AC) for women ≥ 35 years-of-age was replaced with universal NIPT.
Results
When the market price of NIPT (1,077 PPPUS$) is used, contingent NIPT offered to high-risk women < 35-years-of-age adds 34,907,225 PPPUS$; and for women-35 ≥ years-of-age the universal NIPT leads to 142,785,818 PPPUS$ more cost to the government compared to current strategies. The additional costs with NIPT are partially compensated by the cost-savings due to reduction of the number of invasive tests and procedure related losses (17,826,476 PPPUS$ for women < 35-years-of-age and 37,070 PPPUS$ for women ≥ 35-years-of-age). Results are sensitive to the NIPT costs; with a lower cost of NIPT, a total saving would be 33,116,046 PPPUS$ with new strategies.
Conclusions
NIPT might be the choice of prenatal screening strategies if its price is lowered to economically acceptable levels. Until that time, currently accepted protocols seem to be more realistic. On the other hand, decision makers should also consider possible savings and the women's quality of life that can be improved with the new technology.
... [5][6][7][8][9][10][11][12][13][14][15] However, it may vary between different ethnicities as well as by age group. [16][17][18] According to the Fetal Medicine Foundation (FMF) proposed screening, patients with a risk lower than 1:1,000 are classified as low risk and are reassured. If we include the additional ultrasound marker of the presence of nasal bone and Doppler of the venous duct, the cut-off point for highrisk patients will be 1:100. ...
Objective The main objective of this study was to examine the diagnostic performance of the first-trimester combined test for aneuploidies in unselected pregnancies from Rio de Janeiro and compare it with the examples available in the literature.
Methods We investigated 3,639 patients submitted to aneuploidy screening from February 2009 to September 2015. The examination is composed of the Fetal Medicine Foundation risk evaluation based on nuchal translucency evaluation, mother's age, presence of risk factors, presence of the nasal bone and Doppler of the ductus venous in addition to biochemical analysis of pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β−hCG) markers. The cut-off point for high risk for aneuploidies was defined as greater than 1:100, with intermediate risk defined between 1:100 and 1:1,000, and low risk defined as less than 1:1,000. The variable aneuploidy was considered as a result not only of trisomy of chromosome 21 but also trisomy of chromosomes 13 and 18.
Results Excluding the losses, the results of 2,748 patients were analyzed. The first-trimester combined test achieved 71.4% sensitivity with a 7.4% false-positive (FP) rate, specificity of 92.6%, positive predictive value (PPV) of 6.91% and negative predictive value (NPV) of 99.76%, when the cut-off point considered was greater than 1:1,000. Through a receiving operating characteristics (ROC) curve, the cut-off point that maximized the sensitivity and specificity for the diagnosis of aneuploidies was defined as 1:1,860. When we adjusted the false-positive (FP) rate to 5%, the detection rate for this analysis is 72.7%, with a cut-off point of 1:610.
Conclusion The combined test of aneuploidy screening showed a detection rate inferior to those described in the literature for a higher FP rate.
... In the first trimester, risk of aneuploidy is calculated using maternal serum free beta-human chorionic gonadotropin (serum free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, while the risk of trisomy 21 is increased with low PAPP-A values [9]. In the second trimester, serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), hCG, and inhibin-A (inh-A) are utilized [10]. ...
Introduction: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters.
Materials and methods: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests’ parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated.
Results: Fetal chromosomal polymorphism prevalence was 5.3% (n = 101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n = 55); 8.9% (n = 9), and 6.9% (n = 7), respectively]. The most common polymorphic variant was 9qh+ (n = 23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p = .028) and higher unconjugated estriol (uE3) (p = .019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p = .048) or women having fetuses with normal karyotype (p = .007).
Conclusions: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.
Objective
To analyse the prevalence of fetal and infant deaths due to birth defects in Korea and those trends according to maternal age.
Design
Retrospective national cohort study
Setting
Korean Vital Statistics database of the Korean Statistical Information Service, between 2009 and 2015.
Participants
2176 infant deaths and 4343 fetal deaths caused by birth defects, among 3 181 145 total live births and 43 385 fetal deaths during the study periods.
Methods
Infant and fetal mortality rates (IMRs and FMRs) by birth defects, from deaths caused by birth defects, were analysed. They were compared, according to maternal age groups: (I) ‘10–19 years’; (II) ‘20–29 years’; (III) ‘30–34 years’; (IV) ‘35–39 years’; and (V) ‘40–55 years’.
Main outcome measures
IMRs and FMRs by birth defects and comparison according to maternal age group.
Results
IMRs and FMRs by birth defects were 6.84 per 10 000 live births and 13.47 per 10 000 total births. The most common causes of infant deaths and fetal deaths by birth defect were anomaly of the circulatory system (51.1%, IMR 3.5) and chromosomal abnormality (33.1%, FMR 4.46), respectively. Among groups by maternal age, FMRs by birth defects were significantly higher in groups I and V compared with group III (OR 6.59, 95% CI 3.49 to 12.43; and OR 3.46, 95% CI 1.77 to 6.78, respectively). IMR and FMR by nervous system anomaly were significantly higher in group I at 3.63 (OR 2.0, 95% CI 1.97 to 2.03) and 29.84 (OR 15.04, 95% CI 3.59 to 62.96) compared with 0.32 and 1.97 in group III.
Conclusion
FMRs by birth defects were the highest in the extreme maternal age groups. Severe anomalies, except for chromosomal abnormality, were most prevalent in teenage pregnancies.
