Lectures on prenatal malformation diagnosis

2021-03-20 12:00 AM

In the family, there is someone suffering from an inherited disease, pay special attention to genetic diseases related to sex, metabolic diseases and some inherited immunological deficiencies

The purpose of prenatal diagnosis is to detect fetal abnormalities (malformations, chromosomal abnormalities, infections, developmental delay) in order to minimize the possibility of abnormal babies. to varying degrees of criticism. Thus, prenatal diagnosis allows some couples at risk to still have a normal child. Antenatal leg is a technique that has been in development for 30 years. Today, prenatal diagnosis focuses on bleeding-free investigations, molecular biology techniques and pre-factor diagnosis (preimplantation diagnosis).

Coupled with prenatal diagnosis is genetic advice that identifies at-risk couples and provides them with relevant information about prenatal diagnosis.

Prenatal diagnosis is based on medical techniques aimed at detecting the pathology of the embryo or fetus while still in the uterus.

Couples are at risk

Factor of the couple themselves

Mother's age :

This is the most common and the most common indication of prenatal diagnosis. For a long time, it has been known that the mother's age loves the risk of chromosomal abnormalities, the frequency of which chromosomal potential abnormalities vary with the age of the mother (table).

Board. The rate of chromosomal potential abnormalities according to the mother's age

Mother's age

BaTNS 21 (%)

BaTNS 18 (%)

Ba TNS 13 (%)

























Currently, many countries have a policy to make prenatal diagnosis for all pregnant women over 35 years old (USA, Canada) or over 38 years old (France), fully covered by the health insurance system.

Wife or ch yet have abnormal chromosomes (usually in the form of equilibrium deny that ) :

This risk is also common with an ratio of about 1/600 (or 1/300 pairs) according to Lansac. Clinically common pattern of recurrent miscarriages, especially early miscarriages in the first quarter. Parental interoperability leads to an 11% risk of birth defects of the infection. sharp.

Husband or husband had deformed :

This is a compelling reason to undergo a prenatal diagnosis when a wife is pregnant and wants to have a baby.

Abnormal history of children

Child with a chromosomal abnormality: genetic advice allows to evaluate the risk of the next child. About 0.65% of babies are born with chromosomal abnormalities of varying degrees. If there is an abnormality in the number of chromosomes, the risk of the next child is low. If there is an abnormality in the dichotomous structure, the parent's caryotyp should be tested.

History of stillbirth: if it is determined that the cause of stillbirth is due to chromosomal dysplasia, genetic advice should be given to the next pregnancy. Therefore, examination for stillbirths such as: autopsy, bacteria test, vegetable cake test, caryotyp (from amniotic fluid, umbilical cord, skin, organization, fetal blood) is always necessary. If carytyp of dead fetus is disturbed, it is indicated as caryotyp for both mother and father.

Board. The incidence of chromosomal disorders in cases of fetal failure

Gestational age (weeks)

The incidence of chromosomal abnormalities

< 8












Dead after 28 weeks


Newborn death


(theo Angell RR., Sandison A., Bain AD)

Abnormal family history

In the family there is a person with dullness, mental retardation, possibly related to Down syndrome.

In the family, there are people suffering from genetic diseases, special attention should be paid to sex-related genetic diseases, metabolic diseases and some inherited immune deficiencies.

Screened through maternal serum response

Screening is a method of finding a small group of high-risk individuals in a large population. Quantification of maternal serum a-fetoprotein is the first to allow targeting of fetal neural tube defects, fetal wall. Currently in many places, a set of three tests: phCG, a-fetoprotein and triple marker screening are applied in maternal serum to count the limited risk that the fetus will have some deformity. On the basis of the limited risk, further investigations can be made such as hair biopsy, amniocentesis ... In addition, it is possible to quantify some other tracer in the mother's serum to help towards fetal malformations.

Board. Down detection rate using 3 tests (risk limit 1/200)

Mother's age

Detection rate (%)

Fake positive (%)
















(According to Haddoiu JE., Palomaki GE., Knight GJ and CS)

Prenatal diagnostic ultrasound

Ultrasound diagnosis of fetal malformations

Using more and more widely, more and more perfect technology allows early detection of fetal deformities, making ultrasound become the main factor of the prognostic leg.

Before making a decision, it is always necessary to confirm the diagnosis by a very experienced sonographer at an intensive ultrasound facility.

This ultrasound is intended to confirm detected deformities, find possible embryonic deformities, decide whether more exploration is needed (rancidity, caryotyp). Based on this information, a professional committee includes scientists from many fields such as obstetrics and gynecologists, sonographers, pediatricians, geneticists, pediatric surgeons. Practice discussing to find the appropriate management attitude:


Implementing intervention for the fetus right in the uterus, continuing to let the fetus develop.

Plan to deliver and intervene immediately after delivery.

Then the decision of the professional council is informed by the antenatal doctor to the couple.

Table: Sensitivity of ultrasound to diagnose some common fetal malformations (from Boog)





Intracranial pregnancy

100% (n = 155)

Posterior urethral valve

100 % (n = 13)

Spina bifida

89% (n=155)

Atrophy of the esophagus

33% (n=13)

Tho√°t no

90 (% (n=10)

Bowel atrophy

90% (n = 30)


98 % (n = 100)

Diaphragmatic hernia

83% (n = 12)

The fore brain does not split

92% (n = 24)

Umbilical hernia

92 % (n = 72)

Polycystic kidney

89 % (n = 9)

Heart malformation

41% (n = 70)


85 % (n = 67)

Chi malformation

85 % (n = 71)

No kidneys

91% ( n = 34)

Chromosomal abnormality

50 % (n = 36)

The sensitivity of the ultrasound in diagnosis of fetal malformations is quite high, reaching about 95% with the condition performed by an experienced sonographer in a rather intensive center and in situations with suggestive factors ( family history, clinical or biological abnormality ...). This sensitivity will drop to around 55% or even 34% with some undetectable malformations in the context of mass ultrasound. It is known that ultrasound only allows to detect 0.8% of 3% of malformed babies born each year and the false positive rate of ultrasound is about 5 or 6%.

Best ultrasound results in case of a directed ultrasound. During mass ultrasound, it was found that 90% of babies with maternal malformations had no special history.

Heterozygous (central nervous system form: ultrasound is reliable except for spina bifida. Ultrasound results are better if combined with further probe such as alpha-fetoprotein, acetylcholinesterase.

Gastrointestinal tract malformations: ultrasound accurately diagnose except atrophy of the esophagus. At the beginning of the second quarter, it is possible to detect uterine herniation and abdominal wall enlargement, intestinal atrophy can be detected after 26 weeks or 29 weeks when the fetus swallows enough amniotic fluid.

Cardiac malformation: only detects deformities that change many structures of the heart. The 4-chamber section of the heart and the large blood vessels allows confirmation of a normal heart in the vast majority of cases. There are some late acquired heart diseases, normal heart ultrasound at 20 weeks does not guarantee a normal baby's heart birth. The diagnostic sensitivity is about 85% when the fetus has a risk factor, reaching about 60% with a mass ultrasound.

Fetal limb malformations: can only be detected when performing a series of fetal measurements, analyzing bone acoustics, curvature and fractures. Ultrasound at 20-22 weeks gestation allows to observe the most easily pregnant limbs. In the third quarter, the scans have valuable diagnostic help.

Pathology of urinary organs: common, accounting for 1/3 of the total malformations diagnosed before birth. Most of the urinary malformations are detected in the second or third quarter. Prenatal prognosis allows abortion (suspension of pregnancy) if it is a fatal deformity such as the absence of kidneys or Potter's syndrome or requires special care after delivery. Malformations of the urinary organs can be divided into four groups:

Renal malformation: ectopic, polycystic, no kidney ...

Abnormalities of pyelonephric and ureter: water retention kidney, lost ureter, two ureters.

Bladder malformation: no bladder, bladder is protruding.

Urethral malformation: posterior urethral valve, bladder enlargement.

It is necessary to do an ultrasound twice. Many studies have demonstrated that 50-72% of malformations are detected only in the third quarter, especially urinary and digestive malformations. Early ultrasound, the first time around 12 weeks or around 22 weeks, allows the detection of deformities that cannot be corrected. A 32-week-round late-round ultrasound detects reversible malformations. In the absence of a chromosomal abnormality, a team of specialists from many disciplines will discuss the attitude of obstetric management for delivery and management of the baby after birth.

Ultrasound and chromosomal abnormalities

Ultrasound with clinical or biochemical findings increases the effectiveness of predicting chromosomal abnormalities.

Nonspecific signs :

Around the nape of the nape or nape thickness> 3 mm, the lymphoid follicle thinks of a chromosomal abnormality and suggests a caryotyp test.

The dehydration of vegetable cakes in the first quarter evokes the triploid triangle.

Abnormal volume of amniotic fluid such as poly amniotic fluid (the thickness of the amniotic fluid is over 8cm) or the minimum amniotic fluid (the thickness of the amniotic fluid is less than 1cm). Of these, about 3.7% are chromosomal abnormalities.

The umbilical cord has only one umbilical artery (2.7-14% have chromosomal abnormalities).

If the fetus develops with delay in utero, especially the harmonic form (all sizes of the fetus are reduced), 5.6-7.1% has chromosomal abnormality, if poly amniotic fluid is included, the risk increases. 20%.

The femur is short in 40-60% of trisomy 21.

Eyes close together: suggests trisomy 13.

Board. Maternal malformation combined with risk of chromosomal abnormality (Boog)


Chromosomal abnormality (%)

Cystic chorion




The fore brain is not dichotomous


Small headache


Spini bitida


Atrophy of the esophagus


Duodenal atrophy


Atrophy of the intestine


Umbilical hernia


Defects into the abdomen


Diaphragmatic hernia


Urinary malformation


Heart malformation


Lymphoid cysts


Pleural effusion


Vegetable pregnancy


Fetal abnormalities combined with other malformations


Pure crooked foot


Special signs :

Trisomy 21 often combines the following malformations: abnormally thick nape of the neck, short thigh bones, duodenal atrophy, and heart malformations.

The three common chromosomes 18 are: poly amniotic fluid, folded hands, crooked feet, heart disease, diaphragmatic hernia, and umbilical hernia.

Trisomy 13 is often present: eyes close together, cleft palate, heart disease, excess finger defects, polycystic kidney.

The probe bleeds

Furry biopsy in the first quarter

When gestational age is 9-12 weeks, indicated for:

Caryotyp test.

DNA analysis using molecular biology.

Diagnosis of some metabolic diseases.

Sex diagnosis in some cases of hereditary diseases related to sex (hemophilia ...).

Vegetable hair biopsy has been used clinically since about 1980. The hair hair biopsy technique can be done through uterine contraction, through the vagina or through the abdomen. The fur specimens are tested on chromosomes, some enzymes. The hair can be biopsied through the abdomen or the uterus. The rate of complications of vegetable hair biopsy is about 3-15% depending on the author. It is possible to have a hair biopsy of gestational age earlier (6-8 weeks) or later after 12 weeks.

Sucking amniotic fluid

Early amniocentesis when gestational age is less than 14 weeks, allowing research :

The shed cells of the fetus are found in amniotic fluid (chromosomal, DNA test).

Assay for alpha-íetoprotein, acetylcholinesterase, alkaline phosphatase).

The rate of miscarriage is about 1.4%. Amniotic fluid discharge or vaginal bleeding may occur 1-2%, spontaneously resolve after a few days.

Delayed amniocentesis at the gestational age from 14-20 weeks to study the fetal cells that have fallen into the amniotic fluid and some enzymes ... Using spinal needles of size 20 or 22G. At 15 weeks pregnant, the amount of amniotic fluid is about 200ml :

Under the screen of the ultrasound machine can easily poke the amniotic fluid and use a syringe to suck out about 20-30ml of amniotic fluid for testing (alpha-fetopro-tein, DNA). The rate of miscarriage is about 1-2%.

Umbilical cord blood aspiration

It can be done from gestational age after 20 weeks until full month.

Indications for cord blood aspiration:

Infectious disease.

Chromosomal abnormality.

Diseases of the hematopoietic system.

Metabolic pathology.

Inherited immunodeficiency.

Purpose of the treatment: blood transfusion, platelet transfusion ...

In the late 1970s, umbilical cord aspiration was performed during a colonoscopy. Since the mid-1980s, people have been conducting umbilical cord aspiration under the lead of an ultrasound screen, similar to amniocentesis but with more difficulty.

Diagnosis in advance of nesting

Diagnosis of pre-implantation began in the 1990s, opening up the possibility of extremely early diagnosis of the pathology of the embryo before being transferred into the uterus. After conducting in vitro fertilization, embryo cells are taken to study. Only embryos without pathology were transferred into the uterus. However, this technique requires highly equipped and highly skilled laboratories.

Prenatal diagnosis is part of the prenatal care process for women at high risk of having an abnormal baby. Doing well in predicting birth reduces the number of babies born with anomalies, which is one aspect of eugenics.