Prenatal testing and diagnosis can reveal possible cases of Aneuploidy. It is a routine practice to offer first or second trimester serum screening test to identify fetuses at increased risk of open neural tube defects and chromosomal abnormalities.

1. Prenatal Screening for Fetal Aneuploidy
It is a routine practice to offer first or second trimester serum screening test to identify fetuses at
increased risk of open neural tube defects and chromosomal abnormalities.
Calculation of risk for Down syndrome, trisomy 18 and open neural tube defects (ONTDs) is done by
combination of variables which include biochemical serum markers, maternal age, ethnicity, weight,
diabetic status, smoking habit and if available, nuchal translucency (NT). Depending on the results of
the screening tests, diagnostic tests (amniocentesis, CVS) are offered.
First trimester screening includes pregnancy-associated plasma protein A (PAPP-A) and free human
chorionic gonadotropin. Second trimester quad marker include alpha-fetoprotein (AFP), unconjugated
estriol (uE3), human chorionic gonadotropin (hCG) and inhibin-A. The first blood test is collected
between 10 – 13 weeks and the second between 15 – 20 weeks. Test results are available within 7
days.
After pre test genetic counselling, all pregnant women regardless of age are offered prenatal screening
which depends upon the woman’s gestational age at her first prenatal visit and her age at delivery.
Women at increased risk of having a fetus with a chromosomal abnormality are referred early in their
pregnancy for CVS.
Women anticipated to be 36 years or older at the time of delivery; Woman or her partner who (a) has
a history of a previous pregnancy with Down syndrome, trisomy 18 or trisomy 13; or (b) is a carrier of
a translocation, deletion, insertion, or inversion that increases the risk of having a fetus with an
unbalanced chromosomal complement; or (c) has a history of a previous child with an unbalanced
chromosomal complement; or (d) a woman with a pregnancy conceived by IVF with ICSI.
Women 35 years or older with NT > 3.0 mm; or women who are less than 35 years with NT > 4.0 mm
are offered counselling and diagnostic testing without further serum screening.
Consultation with a maternal fetal medicine specialist is recommended for women with an
unexplained low PAPP-A (< 0.4 MoM) in the first trimester or, in the second trimester, an unexplained
elevation of maternal serum AFP ( > 2.5 MoM), hCG ( > 3.0 MoM) and/or inhibin-A ( > 3.0 MoM) or a
decreased level of maternal serum unconjugated estriol (< 0.4 MoM).
MATERNAL SERUM ALPHAFETOPROTEIN
Elevated Maternal Serum AFP (MSAFP)
Unexplained elevation defined as a AFP > 2.5 MoM may be associated with fetal chromosomal
abnormalities, fetal structural anomalies (open neural tube defect, abdominal wall defect), placental
anomalies such as chorioangioma, multiple pregnancy, or fetal demise or maternal conditions such as
ovarian tumour or choriocarcinoma.
Unexplained elevated MSAFP may be due to chorionic villitis and placental vascular lesions. These

2. women are more prone to develop gestational hypertension with proteinuria and adverse features
before 32 weeks’ gestation.
MATERNAL SERUM HUMAN CHORIONIC GONADOTROPIN
Elevated hCG
Unexplained elevation of second trimester hCG varying from > 2.0 to > 4.0 MoM may be due to an
abnormal capillary proliferation that has been associated with in utero hypoxia and confined placental
mosaicism. It is associated with increased perinatal complications such as IUGR, gestational
hypertension with proteinuria, preterm labour and stillbirth.
MATERNAL SERUM UNCONJUGATED ESTRIOL
Low uE3
Defined as ≤ 0.4 MoM
It has been associated with fetal chromosomal anomalies, fetal structural anomalies (anencephaly),
fetal death and fetal metabolic conditions steroid sulfatase deficiency (X-linked ichthyosis), congenital
adrenal hypoplasia/hypocortisolism, Smith-Lemli-Opitz syndrome, and placental aromatase deficiency.
MATERNAL SERUM INHIBIN-A
Its value may be significantly decreased in the presence of primary antiphospholipid antibodies
syndrome and elevated in conditions like triploidy and HELLP syndrome and vanishing twin.
MATERNAL SERUM PREGNANCY ASSOCIATED PLASMA PROTEIN-A
Low PAPP-A
Low maternal serum PAPP-A (< 0.4 MoM) may be of value as an adjunct to ultrasonography in the
prenatal diagnosis of Cornelia de Lange syndrome.
MULTIPLE PREGNANCIES
Screening for trisomy 21 based on maternal serum is not recommended in multiple pregnancies
In twin pregnancies, value of each analyte is about 1.7–2.1 times the value of singleton pregnancy.
Consequently, abnormal elevation of maternal serum AFP and hCG have their cut-offs of ≥ 3.5 MoM
for AFP and ≥ 5.0 MoM for hCG in the second trimester.
Unexplained elevation of AFP and hCG has been associated with increased preterm deliveries and
adverse perinatal outcomes
FACTORS AFFECTING THE LEVELS OF VARIOUS MATERNAL SERUM MARKERS
Maternal factors such as ethnicity, smoking, consanguinity, geographical altitude, hemoglobin level
and fetal gender have been described to have an influencing effect on the maternal serum markers.
Pregnancies with assisted reproductive technologies have been associated with increase in hCG levels.

3. Presence of placenta previa
Elevated MSAFP with placenta previa significantly increases the risk of abnormal decidual invasion and
should increase the index of suspicion for placenta accreta, increta, or percreta.
Article Source: fetalandgeneticclinic.com/prenatal-screening-fetal-aneuploidy/