Fetal monitoring and prenatal diagnosis

Published on 01/03/2015 by admin

Filed under Basic Science

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1199 times

75

Fetal monitoring and prenatal diagnosis

Biochemical tests have limited value in monitoring fetal development, but some components of maternal blood and urine and amniotic fluid may be measured to give evidence of pathology.

HCG

Human chorionic gonadotrophin (HCG) is a glycoprotein produced by the chorionic cells of the developing embryo that is detectable by sensitive assays within days of conception. Measurement of HCG is used to confirm pregnancy, and forms the basis of pregnancy tests (p. 9). The protein’s rapid rate of synthesis in early pregnancy provides systemic evidence of the blastocyst 24 hours after implantation. HCG continues to be secreted by the developing placenta, and serum and urine concentrations increase during the first 9 weeks of pregnancy, then decline gradually until the third trimester (Fig 75.1). The function of HCG is to maintain the activity of the corpus luteum sustaining progesterone synthesis. Measurement of HCG is also of value in:

Prenatal diagnosis

Prenatal diagnostic techniques fall into two groups: invasive and non-invasive (Table 75.1). Prenatal diagnosis may be required because of increased risk of inherited disease. Neural tube defects cannot usually be predicted by family history, and pregnant women may be offered a screening test to detect these disorders. For further details on antenatal screening see pp. 154–155.

Table 75.1

Techniques for prenatal diagnosis

Invasive Amniocentesis
  Chorionic villus sampling
  Cordocentesis
  Fetoscopy
  Fetal skin biopsy
  Fetal liver biopsy
Non-invasive Ultrasound
  Radiography

Alpha-fetoprotein

Alpha-fetoprotein (AFP) is a small glycoprotein synthesized by the yolk sac and fetal liver and is a major fetal plasma protein. Because of its size it appears in fetal urine, and hence it is present in amniotic fluid and maternal blood. AFP concentrations increase in maternal blood until 32 weeks of gestation in a normal pregnancy (Fig 75.2).

Detection of higher than normal AFP concentrations can suggest CNS defects such as anencephaly or spina bifida early in pregnancy, because such malformations of the neural tube are associated with leakage of plasma or CSF proteins into amniotic fluid and consequently maternal serum AFP concentrations increase. In some countries all pregnant women in antenatal care are given the opportunity to have their serum AFP measured between 16 and 18 weeks of gestation, with appropriate counselling. When a high result is obtained, the test must be repeated on a fresh sample. Once other possibilities for an elevated AFP, such as wrong dates or multiple pregnancies, have been excluded, an amniocentesis is performed and the AFP determined in amniotic fluid. High levels suggest the presence of a neural tube defect.

Amniotic fluid acetylcholinesterase (an enzyme found in high concentrations in neural tissue) is also used in some centres to detect fetal malformations.

Serum AFP and HCG concentrations and maternal age may be considered together to assess the risk that chromosomal disorders such as Down’s syndrome are likely to be present. If the risk is high then amniocentesis may be performed to obtain cells for karyotyping.

Cells for study of inborn errors may be obtained either by biopsy of the chorionic villus, which is genetically identical to the fetus, or by culture of cells from amniotic fluid. The latter process takes 3–4 weeks. Both enzyme studies and DNA analysis may be carried out on these tissue samples.

Bilirubin

Bilirubin is measured in amniotic fluid to aid in the assessment of fetal risk in rhesus incompatibility. Incompatible red cell antigens can enter the maternal circulation either from the fetus at the time of delivery or, rarely, because of incompatible blood transfusion; specific red cell antibodies are stimulated in the mother. If a Rh –ve mother has a Rh +ve child these antibodies may cross the placenta and react with specific antigens to the fetal red cell membrane causing haemolysis (Fig 75.3). This is unusual in a first pregnancy but may be a feature of subsequent pregnancies. Excess breakdown of red cells leads to anaemia, overproduction of bilirubin and, eventually, oedema.

During fetal life, unconjugated bilirubin crosses the placenta and is removed by the mother, so the baby may not be born with obvious jaundice. However, the baby will rapidly become jaundiced in the days immediately after birth. In utero, the level of bilirubin in the amniotic fluid can be used to predict the severity of the fetal condition. Amniocentesis is performed on women who have previously had an affected fetus and on women who show a high and rising Rh titre. The severity of the problem can be assessed by reference to a nomogram that relates bilirubin levels to gestational age, such as that in Figure 75.4. Fetal exchange blood transfusion or early delivery may be considered.

Case history 61

A 30-year-old woman who had previously delivered one live child and had one miscarriage attended for antenatal care. She was known to be rhesus negative. At 30 weeks’ gestation she was found to have a high titre of anti-D antibodies.

Comment on page 170.

Rhesus incompatibility is much less common nowadays since susceptible women are given an intravenous injection of anti-rhesus antibody at the time of delivery to eliminate fetal red blood cells that may have entered the maternal circulation. As a consequence they do not survive long enough to be recognized as foreign antigens in the mother. However, haemolytic disease of the newborn cannot be completely eliminated, because it may be caused by other blood group incompatibilities.

Fetal blood gases

Hydrogen ion concentration, blood gases and serum lactate concentration can be measured in fetal blood. Such measurements are only requested when non-invasive investigations have indicated that the fetus is at risk. Fetal blood can be obtained by the technique of cordocentesis, where the blood is sampled from the umbilical cord through a fine needle inserted through the abdomen under ultrasound guidance.

Hydrogen ion concentration can also be measured in fetal blood to assess fetal distress during labour. Capillary blood samples can be obtained directly from the baby’s scalp once the cervix is sufficiently dilated. Fetal hypoxia causes a lactic acidosis and elevated hydrogen ion concentration. Measurement of fetal PO2 can be obtained directly using a transcutaneous oxygen electrode.

image Clinical note

Fetal ultrasound scanning, related to time of conception and/or sequential measurements, has become the most widely used way of monitoring fetal growth. This technique has superseded many biochemical tests of fetal well-being that were once commonly performed.

Fetal monitoring and prenatal diagnosis

Related posts:

Diagnosis and monitoring of diabetes mellitus Adrenocortical pathophysiology The use of the laboratory Screening the newborn for disease Hyperkalaemia Cerebrospinal and other body fluids