July 1993, Volume 43, Issue 7


Prenatal Diagnosis

Nuzhat Rafiq  ( PMRC Research Centre, Jinnah Postgraduate Medical centre, Karachi. )

Growing recognition of frequency and importance of congenital disorders, with current social trends towards smaller families and delays in child bearing, prenatal diagnosis has become very important in the management of many pregnancies. Counselling before prenatal diagnosis is important, prospective parents should understand that a specific diagnosis can be excluded or established with a high degree of reliability but not with complete certainty. One of the most important goals is to help parents understand the reproductive options available to them. Person’s previous experience, ethics, cultural background and religious beliefs will affect the acceptability of prenatal diagnosis and choice to be made, if any abnormality is detected. Congenital defects account for a high mortality in newborn and serious morbidity in infancy and child­hood1. The identification of pregnancies in which there is an increased chance of diagnosable fetal disorder in­volves a search for general and specific risk factors. Age is identified as one of the important general risk factors. Prenatal cytogenetic diagnosis should be offered to all women who will be 35 years of age or over, at their expected date of delivery, as the frequency of numerical chromosomal abnormality increases with advancing age2. Tests for biochemical markers in maternal serum identify babies at risk for certain cytogenetic and structural abnormalities . Alpha-fetoprotein is synthe­sized in fetal liver and yolk sac in early fetal life. Its level is increased in maternal serum and amniotic fluid if the fetus has open neural tube or ventral wall defects associated with the exposed fetal membranes or blood vessels3. Invasive procedure such as amniocentesis elevates the maternal serum level of alpha-fetoprotein, so blood sample for screening should be collected before such procedure. Low levels of serum alpha-fetoprotein and un­conjugated estriol are associated with trisomy 21 and trisomy 184. Significantly elevated levels of human chori­onic gonadotropin is the single marker that yields the highest detection rate for Down’s syndrome. Combined use of maternal serum, human chorionic gonadotropin and unconjugated estriol levels, alpha- fetoprotein level and maternal age can identify approximately 60% of Down Syndrome cases with a false positive rate of 6.6 which is reduced to 3.8 by use of ultrasonography to verify gestational age5. Specific risk factors may be identified in the family history, history of previous pregnancies or the mothers’ medical history. After the birth of one child with trisomy 21, for example, the likelihood that a subsequent child will have a similar chromosomal abnormality is approxi­mately 1 percent, the rate of recurrence of a neural tube defect is 2-5 percent as compared with arate of 2 per 1000 births in general population6. If the parents have spinabifida, congenital heart disease or any known chromosomal translocation, there is an increased chance that child will have related defect7. Prenatal diagnosis is important for many inborn errors of metabolism, almost all of which are transmitted in an autosomal recessive fashion. Diabetes mellitus or phenylketonuria in the mother are associated with an increased risk of fetal malformation. Known teratogens include ionizing radiation, therapeutic and illicit drugs and maternal infections. Important procedures for prenatal diagnosis in­clude amniocentesis, chorionic villous sampling, percu­taneous umbilical blood sampling, fetal biopsy and ultrasonography. Amniocentesis with ultrasound guidance is done in 18th week of gestation in outpatient facilities. Chromo­somal studies are carried out by culturing few viable cells present in amniotic fluid and results are generally available in 10 to 14 days8. The fetal mosaicism diag­nosed by chromosomal culture studies is rare but clinically very important9. This can be further confirmed by karyotyping fetal blood sampling, which provides results within 48 hours10. Chorionic villous sampling can be done through a transcervical catheter or transabdominal needle with ultrasound guidance. Choice of location depends upon the location of placenta and operator’s experience and performance. Main advantage of chorionic villous sam­pling over amniocentesis is the earlier availability of results because procedure is done at 9-12 weeks of gestation. The greater frequency of contamination by maternal cells and pseudomosaicism in chorionic villous sampling contribute to the reduced cytogenetic accuracy of this procedure as compared with amniocentesis. A woman assigned to villous sampling has a lower chance of successful pregnancy outcome than a woman having 2nd trimester amniocentesis11. The clinical disadvan­tages of increased risk and potential diagnostic error with chorionic villous sampling should thus be weighed against the disadvantages of later timing of amniocente­sis. Percutaneous umbilical blood sampling was devel­oped for the diagnosis of toxoplasmosis. It is done at about 18th week of gestation with 20-22 gauge spinal needle inserted under ultrasound guidance into umbili­cal cord. Access to the fetal circulation permits the prenatal evaluation of many fetal haematologic abnor­malities, including isoimmunization, haemoglobin-op­athy, thrombocytopenia and coagulation factor abnor­malities12. Fetal blood can be used for prenatal diagnosis of some inborn errors of metabolism, assessment of viral, bacterial and parasitic infection and to clarify whether chromosomal mosaicism detected by amniotic fluid or chorionic villous sampling is truly present or not. As percutaneous umbilical blood sampling entails a substantially greater risk of pregnancy loss than amnio­centesis, it should be reserved for cases in which rapid diagnosis is essential or diagnostic information cannot be obtained by safer means. Fetal biopsy is a rare procedure performed with ultrasound guidance for the diagnosis of genetic disorders like epidermolysis bullosa and Duchenne’s muscular dystrophy13. Ultrasound is an important and most commonly used aid now-adays, specially in our country, for the assessment of gestational-age, fetal growth monitoring, placental site, detection of multiple gestation and the diagnosis of major fetal anomalies. Some teratogens and infections produce only structural abnormalities which are potentially detectable with ultrasound only, visualiza­tion of fetal anatomy is essential in diagnosis of anatomi­cal defects inherited in polygenic on multifactorial fashion. Ultrasound has also shown impressive achieve­ment in diagnosing renal and bladder anomalies, hydro­cephaly, neural tube and ventral wall defects14. It is also useful in mandelian’s disorders characterized by certain anatomical defects, such as skeletal dysplasias. The most common congenital abnormalities are cardiovascular malformations, that is commonly missed in prenatal ultrasound examination. A four chamber view of the fetal heart is suggested for ultrasound examination in pregnancy and its sensitivity, for the detection of congenital heart defect is reported to be very high in referred population15. When any fetal anomaly is diag­nosed ultrasonographically, echocardiography should be performed because such fetuses have 23% risk of cardiac defect16, conversely fetuses with cardiac defect have 25-45% risk of having any other anatomical defect. One third of such fetuses will have chromosomal disorder. When fetal abnormalities are detected at any stage of prenatal period, consultation can be sought with a multidisciplinary team of physicians, ethicists, nurse specialist and psychologist to plan management The appropriate personnel, location and mode of delivery should be determined to reduce the risk of complications and danger to mother’s and fetal life as much as possible.


1. Contribution of birth defects to infant mortality- United States, 1986. MMWR Morb. Mortal. Wkly. Rep., 1989;38:633-35.
2. Hook, E.B. Rates of chromosome abnormalities at different maternal ages. Obstet. Gynecol., 1981;58:282-85.
3. Maternal serum-alpha-fetoprotein measurement in antenatal screening for an­encepbalyand apinabifida inearly pregnancy. Report of the U.K. CollaborativeStudyon Alpha-fetoprotein in relation to neural-tube defects. Lancet, 1977;1:1323-32.
4. Merkatz, I.R., Nitowaky, H.M., Macri, J.N. and Johnson, W.E. An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalitiea. Am.J.Ob­atet. Gynecol., 1984;148:886-94.
5. Haddow, J.E., Palmaki, G.E., Knight, G.J. etaL Prenatal screening for Down\\\'s syndrome with uae of maternal serum markers. N. Engl.J.Med., 1992;327:588-93.
6. Stene, J.Detection ofhigberrecurrencerisk for age-dependent chromosome abnormal­ities with an application to trisomy G1 (Down’s syndrome). Hum. Hered., 1970;20:J12­-22.
7. Lin, A.E., and Carver, K.L., Geneticcounselling forcongenital heartdefecta. 3. Pediatr., 1988;113:1105-9.
8. The NICHD National Registry for Amniocentesis Study Group. Midtrimeater amnio­centesis forprenatal diagnosis; safety and accuracy. JAMA., 1976;236:1471-76.
9. Hau, L.Y.F., Perlia, T.E. United States aurvey on chromosome mosaicism and pseudombaaiciam in prenatal diagnoaia. Prenat. Diagn., 1984;4:97-130.
10. Goaden, C., Nicolaidea, LU. and Rodeck, C.Fl. Fetal blood sampling in investigation of chromosome moaaiciam in amniotic fluid cell culture. Lancec, 1988;1:613-17.
11. Canadian Collaborative CVS-Amnioeenteaia Clinical Trial Group. Multicentre randomiaed clinical trial of chorion villua sampling and amniocentesis; first report. Lancet, 1989;1:1-t
12. Deffos, F., Capella-Paviousky, M. and Foreatier, F. Fetal blood aampling during pregnancy with uae of a needle guided by ultrasound: a study of 606 conaecutive cases. Am.J. Obstet. Gynecol., 1985;153:655-60.
13. Evans, M.L, Greb, A., Kunkel, LM. et aL In utero fetal muscle biopsy for the diagnoaia of Duchenne muscular dyatropby. Am.). Obatet. GynecoL, 1991;165:728-32.
14. DAlton, M, Romero, it, Grannum, P., DePalma, L, Jeanty, P. and Hobbina, J.C. Antenatal diagnosis ofrenal anomalies with ultrasound, IV. Bilateral multicyatic kidney disease. AmJ.Obatet. GynecoL, 1986;154:532-37.
15. Allan, L.D. Fetal echocardiography. Clin. Obatet. Gynecol., 1988;31:61-79.
16. Copel, J.A., Pilu, 0. and Kleinmin, CS. Congenital heart diaeaae and extracardiac anomalies: associations and indications for fetal echocardiography. Am.J. Obatet. Gynecol., 1986;154:1121-32.

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