Hamdan Medical Journal

: 2022  |  Volume : 15  |  Issue : 2  |  Page : 55--58

Screening for aneuploidies in first trimester: Overview and patient management

Daria Pashkunova, Ayman Tammaa 
 Department Obstetrics and Gynecology, Klinik Floridsdorf, Vienna, Austria

Correspondence Address:
Ayman Tammaa
Department Obstetrics and Gynecology, Klinik Floridsdorf, Vienna


Introduction: First trimester prenatal screening is a risk assessment test which allows to detect pregnancies at increased risk for for most frequent foetal aneuploidies. Methods: A literature review using PubMed was carried out. Results: In this review, we focus on general principles of first trimester screening, assessment of specific sonographic markers and maternal biochemical parameters. In addition, management options are discussed.

How to cite this article:
Pashkunova D, Tammaa A. Screening for aneuploidies in first trimester: Overview and patient management.Hamdan Med J 2022;15:55-58

How to cite this URL:
Pashkunova D, Tammaa A. Screening for aneuploidies in first trimester: Overview and patient management. Hamdan Med J [serial online] 2022 [cited 2022 Aug 19 ];15:55-58
Available from: http://www.hamdanjournal.org/text.asp?2022/15/2/55/349780

Full Text


Each pregnancy has a potential risk of foetal chromosomal anomalies or structural malformations.

Prenatal detection of structural malformations and most frequent aneuploidies in newborns – Trisomy 21, 18 and 13 – changed significantly during the past decades. Initially, only karyotyping of amnion cells collected virtually blindly through amniocentesis with corresponding risks of complications at the earliest in the second trimester was available.

The introduction of ultrasound sonography represents a milestone in obstetrics and had a profound impact on prenatal screening programmes.

 Age-Related Screening Programmes

Since advanced maternal age is associated with a higher incidence of certain aneuploidies and major abnormalities, invasive diagnostic procedures, such as amniocentesis were traditionally offered to every pregnant woman aged >35 years as a screening method. Although the average age of pregnant women is increasing, still 76% of women giving birth are younger than 35 years, according to the Federal Statistics Office in 2019 in Austria.[1] However, this patient's group was excluded from screening for foetal aneuploidies. As a consequence, the majority of aneuploid pregnancies were not recognised in age-related screening.[2]

 General Principles

The first-trimester screening (FTS) is a risk assessment test and includes maternal factors, detailed ultrasound scan with the evaluation of special sonographic markers and maternal blood test. The purpose of prenatal screening is to identify women who are at increased risk for foetal chromosomal defects and to offer further prenatal counselling regarding further diagnostic steps if needed. FTS should be done only by officially certified sonographers between 11 + 0 and 13 + 6 weeks of gestation or in pregnancies with a foetal crown–rump length (CRL) between 45 and 84 mm. The basic risk for foetal abnormalities depends on maternal and gestational age. The individual risk is calculated with a variety of likelihood ratios, based on the results of ultrasound examination and maternal blood tests.

The main sonographic marker is the nuchal translucency (NT), whose enlargement indicates an increased risk of chromosomal defects.[3] The measurement of the foetal heart rate helps primarily to distinguish between different aneuploidies.[4] The assessment of new markers, such as nasal bone, ductus venosus flow and tricuspid flow, improves the detection rate of foetal aneuploidies. Altered concentrations of placental products of free beta-human chorionic gonadotropin (ß-hCG) and serum pregnancy-associated plasma protein-A (PAPP-A) in maternal blood are also associated with chromosomal abnormalities.

Apart from the detection of pregnancies with higher risk of chromosomal defects, other important information can be obtained by the FTS:

In case of uncertain date of conception and/or ovulation, measurement of the CRL enables the sonographer to estimate the correct gestational ageFurthermore, it is already possible to diagnose several major foetal abnormalitiesIn the case of twin or multiple pregnancies, FTS is the best opportunity to assess chorionicity and amnionicity, which is highly relevant for the further management of multiple pregnancies. Mono-or dichorionicity is defined by the so-called T-or Lambda-sign, respectively, and can be best seen in the first trimester[5]The Doppler ultrasound of the uterine arteries in combination with the measurement of maternal blood pressure and serum placental growth factor helps to calculate individual risk for pre-eclampsia, to establish appropriate therapy and further monitoring if needed.[6],[7]

 Chromosomal Abnormalities and Major Foetal Malformations

Aneuploidy is the most common genetic abnormality detected by prenatal diagnostics.

Chromosomal anomalies, detected by FTS and their prevalence are shown in [Table 1].[8]{Table 1}

Due to the small CRL, the early detection of foetal malformations is limited, however, using a standardised anatomical protocol enables the sonographer to detect several foetal defects irrespective of aneuploidies [Figure 1].[9],[10]{Figure 1}

 Nuchal Translucency

The measurement of the NT is a milestone in prenatal diagnostics. Numerous studies have proven, that its use as a component of FTS raises the detection rate of affected foetuses.[11]

NT is the clear space behind the foetal neck, which appears in ultrasound as a collection of fluid between the spine and skin edge [Figure 2].{Figure 2}{Figure 3}

The optimal cut-off for foetal NT has been investigated in different studies and could be either adjusted for gestational age or fixed, which means CRL-dependent or independent. In case of a fixed cut-off, a foetal NT >3.0 mm should be followed by a recommendation for further diagnostic steps.[12],[13] Using the age-adjusted cut-off, increased NT is defined as NT exceeding the 95th percentile.[3]

Enlarged measurement of NT is not only associated with chromosomal defects but also with a variety of other pathological conditions, other than aneuploidy. In this case, extraordinary diligence must be taken by the sonographer during the second-trimester screening. However, if no other anomaly is present, the NT usually resolves during the second trimester, and the majority of those foetuses have a favourable outcome.[14],[15]

 Foetal Heart Rate

Physiologically, the FHR increases between 5 and 9 weeks of gestation and then consequently decreases from approximately 170 bpm at 9 weeks to 150 bpm at 14 weeks. The deviation of FHR from the norm could indicate a foetal heart failure.[16] Since all chromosomal defects are associated with heart failures, the measurement of FHR was demonstrated to be a good additional marker.[4] The high FHR is profoundly associated with trisomy 13 – in 85% of cases, it is >95th percentile.[17] In foetuses with trisomy 21, the FHR could also be increased. In contrast, foetuses with trisomy 18 show decreased FHR.[4]

 Nasal Bone

An absent or a hypoplastic nasal bone serves as a soft marker for foetal aneuploidies and is associated in 60% with trisomy 21, 18 and 13 in 60%, 50% and 40%, respectively. However, if it occurs isolated, the outcome is reported to be favourable.[18]

 Ductus Venosus

The ductus venosus is an essential part of foetal circulation. This small vessel is a physiological shunt, which allows the oxygenated blood in the umbilical vein to bypass the liver and ensure the optimal oxygenation of the foetal brain.[19] If the blood flow in the ductus venosus appears pathological, a higher risk of cardiac anomalies and a higher risk of aneuploidies must be assumed.[20] If chromosomal anomalies have been excluded, the detailed ultrasound examination in the second trimester is required to exclude or diagnose major heart failure. However, in about 80% of the cases, the pregnancy outcome is still normal.

 Tricuspid Flow

It has been shown that the assessment of flow across the tricuspid valve can improve the detection rate of foetuses with aneuploidy. Normally, the flow shows no regurgitation during systole. However, if the tricuspid flow is pathological, the risk of major cardiac defects is increased with a prevalence of about 4–1000.[21]

 Serum Biochemistry

To improve the accuracy of the first-trimester scan for the detection of aneuploidies, it can be combined with the measurement of certain placental products in the maternal serum: ß-hCG and serum PAPP-A serve as additional factors to assess the individual risk for aneuploidies. The first-trimester scan and assessment of those two maternal serum parameters are known as 'combined test'.

Essentially, to interpretate measured levels of ß-hCG and PAPP-A, their values are first adjusted to an expected normal multiple of the median (MoM). Levels of ß-hCG and PAPP-A in current pregnancy are divided by levels expected in a normal pregnancy of same maternal parameters. In euploid pregnancies, the average fß-hCG is 1.0 MoM and PAPP-A is 1.0 MoM. However, in aneuploid pregnancies, the level of PAPP-A tends to be lower. Fß-hCG is observed to be higher in pregnancies with trisomy 21 and Turner syndrome. In contrast, fß-hCG levels are significantly lower in pregnancies with trisomies 13 and 18.[22] Recent data also show that the prevalence of abnormal chromosomal foetal findings increases with PAPP-A <0.2 MoM and fß-hCG <0.2 order >5 MoM.[23]

 Interpretation and Management

After the measurement of all parameters, the individual risk is calculated using a special algorithm. A screen positive test result indicates that the individual's risk of having a child with aneuploidy is equal to, or exceeds a specific cut-off level. Several studies differentiate between women at high risk or low risk for aneuploidy with a cut-off risk of 1/300. The so-called contingent screening is a new approach, which is characterised by dividing pregnant women into three groups: high, intermediate and low risk. While women in the high-risk group are advised to have invasive diagnostic interventions such as amniocentesis or chorionic villus sampling, women who belong to the intermediate-risk group, are recommended to have a non-invasive prenatal test (NIPT) to analyse foetal cell-free DNA (cfDNA). Foetal cfDNA derives from the foetus, is released from the placenta and can be detected as soon as 10 + 0 weeks of gestation in the maternal blood.[24] NIPT has a higher sensitivity and specificity for the detection of trisomies 21, 18 and 13 compared to the combined test.[25] It identifies 99% of trisomy 21 and with a false-positive rate of 0.1%. For that reason, NIPT is used in patients with intermediate risk.[26]

However, non-genetic malformations cannot be detected by the NIPT.[27]


All women should be offered aneuploidy screening or diagnostic testing during pregnancy, regardless of pre-existing risk factors.

Constantly increasing ultrasound resolution enabled the detection of structural malformations at progressively earlier gestational age and made it possible to develop non-invasive first-trimester-risk-assessment for trisomies 21, 18 and 13, consecutively. Considering specific maternal factors, biochemical serum parameters and ultrasound-Doppler measurements additionally improved early risk assessment for genetic disorders as well as pre-eclampsia and early foetal growth restriction. Lately, modern molecular laboratory techniques introduced estimation of cfDNA fraction in maternal blood sampling into the FTS programme. However, sonography will remain mandatory in the early detection of structural malformations. Advances in ultrasound technique allowed further diagnostic approaches such as sonography-guided chorionic villous sampling already in the first trimester.

Finally, the contingent approach in FTS balances incidence of diseases, risk in the prenatal invasive procedure, cut-off levels, sensitivity/specificity and predictive values of markers and biochemical parameters versus cfDNA evaluation.

Respecting patients 'right not to know' informed consent regarding FTS is essential. Detailed parents' information concerning potential benefits and limitations of each step in FTS policy is required.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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