1st trimester ultrasonographic screening (11+0 - 13+6 weeks of pregnancy)
The first ultrasonographic screening is performed between 11+0 and 13+6 (week+day) of pregnancy. Gestational age is counted from the first day of the last menstrual period. If the gestational age is not known (for example in cases of uncertain date of the last menstrual period, or irregular menstrual cycle), dating of the pregnancy is estimated according to ultrasonographic measurement of the length of the fetus from the top of the head (crown) to the bottom of the buttocks (rump), Crown Rump Length (CRL). As the CRL at 11+0 weeks is about 45 mm and at 13+6 weeks is about 84 mm, the ultrasonographic screening is performed between the CRL values of 45 and 84 mm.
Ultrasonographic screening in this period of pregnancy is sometime called as first trimester screening. This designation is based on presumption that pregnancy lasts 40 weeks in average, which is 10 lunar months (1 lunar month = 4 weeks) or approximately 9 calendar months. The period of pregnancy is then divided into three periods, or "trimesters".
Literal translation of the word "trimester", which comes from Latin, is "three months" and so if we follow lunar months, than the first trimester should last only until the end of the 12th week (3x4 weeks). In this case the designation "first trimester" screening would a bit inaccurate, because in practice we think the period until the 13+6 weeks, which exceeds little bit into the second trimester.
In general, the word screening means searching for a disease or an anomaly in population, using various examinations. First trimester ultrasonographic screening tries to look some structural fetal defects and to identify fetuses with increased risk of chromosomal anomalies such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), Patau syndrome (trisomy 13), or others. These anomalies present with some minor or major structural and hemodynamic changes that are called markers.
In effort to increase detection rate of chromosomal anomalies, the ultrasound screening is connected with biochemical screening. The biochemical screening determines levels of some glycoproteins or hormones in maternal blood (PAPP-A - Pregnancy Associated Plasma Protein-A, free β-hCG -;free β-subunit of human chorionic gonadotropin, AFP - alpha fetoprotein, uE3 - unconjugated estriol). Their abnormal levels may increase risk of fetal chromosomal anomalies.
First biochemical screening (PAPP-A, β-hCG) is performed between 10+0 and 12+0 weeks. Every woman carries certain background (or a priori) risk of having her fetus/baby affected by a chromosomal defect (Down syndrome, Edwards syndrome, etc.). The risk depends on maternal age and length of her gestation, and is adjusted to individual (specific for a given woman) risk by multiplying of the a priori risk by a series of likelihood ratios, which depend on the results of biochemical and ultrasonographic exams (combined test).
Ultrasonographic examination between 11+0 and 13+6 weeks of pregnancy provides lot of information. A fetus in this period of pregnancy may show some signs (markers) of chromosomal defects (Down syndrome, Edwards syndrome, Patau syndrome, etc.), and also some structural (morphological) anomalies (gastroschisis, omphalocele, pentalogy of Cantrell, limb defects, anencephaly, and others). Although there are many limiting factors (size of observed structures, position of the placenta and fetus, maternal obesity, etc.), in good echoic conditions even some cardiac anomalies can be diagnosed in this stage of gestation.
Screening for Down syndrome
Down syndrome is the most commonly mentioned anomaly in the context of the first trimester ultrasonographic and biochemical screening. This is because it is one of the most common chromosomal defects and its incidence in fetuses increases with maternal age. That is why traditional screening strategy offered invasive testing (amniocentesis or chorionic villus sampling - CVS), to all women aged more than 35 years. Only these invasive tests provide evidence of Down syndrome (or some other genetic abnormalities included in testing). That is the main difference to the ultrasonographic or biochemical screenings that are just trying to select women with increased risk of genetic abnormalities.
Invasive testing carries approximately 1% (1:100) risk of miscarriage (abortion). Nowadays about 20% of pregnant women are older than 35 years and their invasive testing would lead to many pregnancy losses. Furthermore, this strategy detects just about 50% of cases of the Down syndrome in population of pregnant women, because the rest 50% of the cases is among younger pregnant women. The younger group makes up much bigger part of the pregnant population (about 80%), and so no matter the frequency of the syndrome in this population is lower, the overall amount of cases in this population is also about 50%.
Ultrasonographic and biochemical screenings represent more effective method of selection of the high-risk group women to which invasive testing is offered subsequently. This combined screening adjusts the background risk of a woman undergoing the examination of biochemical parameters (PAP-A, β-hCG) and ultrasonographic scan.
The most important ultrasonographic markers of chromosomal defects are:
- nuchal translucency (NT) measurement (NT is a collection of fluid under the skin at the back of fetal neck - nuchal region);
- evaluation of nasal bones (NB) - their absence or hypoplasia;
- evaluation of fetal heart rate;
- evaluation of the blood flow across the tricuspid valve of the heart (tricuspid regurgitation, TR) and within the ductus venosus (DV; venous connection of the umbilical vein to the inferior vena cava leading to the right atrium of fetus).
Besides these basic ultrasonographic markers, other structural anomalies can sometime be detected, and their presence may also increase the risk of abnormal genetic background of such fetuses.
Nuchal translucency is a collection of fluid under the skin at the back of fetal neck (nuchal region). Certain amount of the fluid is present in this region in all fetuses, but is increased in cases of many fetal anomalies or syndromes. Size of the nuchal translucency can be measured very accurately by the ultrasound, and calculation of the risk of fetal chromosomal abnormalities such as Down syndrome, Edward's syndrome, and Patau syndrome can be done according to the thickness of the nuchal translucency.
76.8% of Down syndrome fetuses (trisomy 21), with a false positive rate 4.2%, have increased nuchal translucency thickness. When nuchal translucency is combined with biochemical screening (PAPP-A, β-hCG), detection rate of fetuses with Down syndrome is increased up to 87.0%, with 5% false positive rate .
There are several patho-mechanisms leading to increased accumulation of fluid under the skin of the nuchal region, and so the widened nuchal translucency may reflect many fetal abnormalities, for example cardiac anomalies, skeletal dysplasias, and already mentioned chromosomal defects (Down's syndrome, Edward's syndrome, Patau syndrome, Turner syndrome, etc).
Nuchal translucency measurement has to follow some well-defined criteria postulated by Fetal Medicine Foundation in London in effort to guarantee high standard of examination on international basis. The foundation certifies physicians an sonographers that are eligible to perform the measurement at desired level.
Evaluation of fetal nasal bones
Up to 73% of fetuses with Down syndrome, but only 0.5% of normal fetuses, have absent nasal bone at 11-14 weeks of gestation . Evaluation of the nasal bones is a part of the first trimester ultrasonographic screening and its absence makes one of the markers of the Down syndrome.
Evaluation of the blood flow in ductus venosus
Ductus venosus is venous connection between umbilical vein (carrying oxygenated blood from the placenta towards fetus) and inferior vena leading to the right atrium of the fetal heart. Blood flow within the ductus venosus can be assessed by Doppler ultrasound. Evaluation of the flow in the ductus venosus is a part of the first trimester ultrasonographic screening.
Abnormal flow within the ductus venosus is present in 70-90% of fetuses with Down syndrome, Edward's syndrome, Turner syndrome, but only in 5.2% of normal fetuses [4-12]. Abnormal flow within the ductus venosus may reflect structural abnormalities of the fetal heart.
Evaluation of the blood flow across the tricuspid valve
Tricuspid regurgitation reflects insufficiency of the tricuspid valve (valve between the right atrium and right ventricle of the heart) to prevent of reversed flow of the blood via the valve from the right ventricle to the right atrium during ventricular contraction. This reversed flow during ventricular contraction can be detected by Doppler ultrasound.
Tricuspid regurgitation is often present in cases of structural anomalies of the heart and is frequently present in fetuses with chromosomal defects (Down syndrome, Edwards syndrome, etc.), because these anomalies are often associated with abnormal development of the heart [13-15]. Some studies have found tricuspid regurgitation in 67.5% of fetuses with Down syndrome, 33.3% of fetuses with Edward's syndrome, but only in 4.4& of normal fetuses .
Intracranial translucence is a first trimester marker of neural tube defects. It is a space of the fourth cerebral ventricle, delineated by the posterior wall brain stem and choroid plexus of the fourth ventricle. This space can't be seen in fetuses with open neural tube defects (spina bifida) [17, 18].
Thorough ultrasonographic examination of the fetus in the first trimester of gestation can sometime reveal the open neural tube defects directly, without need of evaluation of the intracranial translucency.
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