Prenatal diagnosis

• Congenital anomaly


  Caused by genetic and environmental factors
• 1. 6% of live births have congenital anomaly resulting in 21% of infant mortality
• Malformation


  Anomaly of structural formation
• Disruption


  Alteration of already formed structures e.g. amniotic band
• Deformation


  Remolding of formed part by mechanical force e.g. Club feet
• Congenital anomaly may come as a syndrome or an association (VACTERL association)
• Principles of teratology


  • Genetic interaction with environment
  • Developmental stage of exposure
  • Dose of teratogen
  • Duration of exposure
  • Specificity of pathogenesis
  • Varied manifestations
• Class of teratogens


  • Infectious agents; Rubella, Cytomegalovirus, HIV etc
  • Hyperthermic infection: Mumps, Polio, hepatitis etc
  • Radiation: ionizing radiation kill proliferating cells, effect can linger
  • Chemical Agents: this include phamacological agents, e.g. Thalidomide - amelia, anticonvulsants, antibiotics, antihypertensives
  • Social drugs e.g. alcohol, cocaine, cigarette, vitamin A etc
  • Hormones
  • Maternal disease
  • Nutritional deficiency
  • Obesity
  • Hypoxia
  • Heavy Metals
• Technological advancement have led to the possibility of intrauterine fetal testing resulting in possible interventions
• Current diagnostic tests are invasive and very expensive, but they can help confirm diagnoses
• Invasion of the fetal/placental unit poses varied risks
• Chorionic villus sampling and amniocentesis are two most common associated with fetal loss which had declined recently
• Indications for prenatal diagnosis

  • Advanced maternal age (>35 years)
  • Previous history of anomaly
  • Recurrent pregnancy loss
  • Suggestive fetal ultrasonographic findings
  • Positive maternal screening test findings
  • Mother medications or infections
  • Genetic trait in the parents
• Genetic counseling


  An essential adjunct to prenatal diagnosis
• Genetic counseling helps


  • Inform families about the diagnosis, severity, prognosis, and available options for treatment and continuation of pregnancy
  • Helps the family to make informed decision
  • Helps the caregiver to prepare ahead of time
• First trimester


  1. Fetal ultrasonography for anatomical survey traditionally done between 18-22 weeks

  2. Chorionic villous sampling for diagnosis before the 12th week, not for anatomical abnormalities

  3. CVS is done under ultrasound guidance following assessments of viability and location

  4. Approach can be trans-abdominal, trans-cervical or trans-vaginal depending on placental/uterine position

  5. Direct or long-term method can be used depending on the number of days available
• Complications of first-trimester CVS

  • Pregnancy loss; doubled the normal with increased incidence of other anomaly
  • Feto-maternal transfusion, thus, Rh iso-immunization is a relative contraindication
• Early amniocentesis


  1. Done between 14th and 22nd week, preferred to CVS in multiple gestation and biochemical disorders

  2. The procedure consists of the aspiration of amniotic fluid (1ml/wk) from an amniotic fluid pocket with a 22-gauge needle under ultrasonographic guidance
• Complications associated with amniocentesis

  • Uterine bleeding
  • Uterine cramping
  • Leakage of amniotic fluid
  • Pregnancy loss
  • Increased risk of clubfoot when performed prior to 12 weeks' gestation
  • Procedural failure due to tenting of the membranes ahead of the needle
• Pre-implantation biopsy


  • Indicated in women with substantial risk of a known genetic disorder and in women with repeated miscarriages due to chromosomal translocation
  • Done at the eight-cell stage of the embryo or the second polar body
• Coelocentesis


  Defined as coelomic fluid aspiration, done between 6th and 10th week
• Second trimester


  1. Mid-trimester amniocentesis; performed between 16th and 18th week

  2. Preceded by genetic counseling to evaluate genetic risks and detailed ultrasonography to estimate gestation, placental location, and amount of amniotic fluid

  3. As much as 20-30 mL of amniotic fluid is aspirated for analysis for several substances

  4. Fetal cells obtained from the fluid can be analyzed for chromosomal and genetic disorder

  5. Techniques such as (Polymerase chain reaction) PCR and(Fluorescence in situ hybridization) FISH have improved its efficiency, accuracy and promptness
• Complications of second-trimester amniocentesis

  • Pregnancy loss
  • Amniotic fluid leakage
  • Amnionitis
  • Rh iso-immunization
  • Mosaicism on cytogenetic analysis
• Cordocentesis

  1. With ultrasonographic guidance, a sample of fetal blood is obtained from the umbilical vessel close to the cord insertion near the placenta using a 20- to 27-gauge needle

  2. Trans-placental or trans-amniotic can be used depending on placental position

  3. Additional advantage is the assessment of fetal arterial oxygen tension (PaO2), carbon dioxide tension (PCO2), and pH
• Complications associated with cordocentesis

  • Fetal loss
  • Preterm labor
  • Hematoma of the umbilical cord and placental abruption
  • Chorioamnionitis
  • Fetal exsanguination from the procedure site
  • Rh iso-immunization
• Late chorionic villus sampling

  • The technique of placental biopsy allows for karyotyping with small amounts of placental tissue
  • It has the advantage of being as accurate as amniocentesis, and it provides rapid results
• Fetal muscle and liver biopsy

  When previous investigations are non diagnostic
• Third trimester and labour

  1. Amniocentesis; for measurement of pulmonary surfactant and surface-active phospholipids

  2. False results occur in diabetic mother, blood or meconium contamination and intrauterine asphyxia

  3. Non-stress test using Doppler ultrasonography or electrodes on the maternal abdomen/fetal scalp

  4. Biophysical profile test; amniotic fluid volume (AFV), fetal breathing movements, fetal activity, and fetal muscle tone and non-stress test are assessed

  5. Contraction stress test; to monitor fetal heart rate in response to uterine contractions

  6. Doppler study; study of fetal umbilical arterial blood flow velocity or resistance to flow

  7. Ultrasonography; measuring CRL, BPD, FL and abdominal circumference

  8. Magnetic resonance imaging; adjunct to USS, better imaging in oligohydramnios

  9. Computed tomography; limited applications in prenatal diagnosis, delineates fetal bony anatomy better than other imaging modalities

  10. Fetal magnetocardiography; a non-invasive means of monitoring cardiac
• Prenatal diagnosis has changed from terminating the pregnancy to possible intervention for improved gestational outcome
• Medical Fetal Therapy


  • Folic acid for NTDs
  • Replacement therapy with Dexamethasone in CAH
  • Treatment of maternal condition (Thyrotoxicosis, hyperthyroidism) using Propylthiouracil and iodine respectively
  • Maternal HIV treatment with Zidovudine from 14th IUW to 6th PNW
  • Enzyme reactivation by the use of Biotin in carboxylase deficiency
  • Accelerated organ maturation, lung with the use of steroids
  • Correction of iso-immunization with prenatal transfusion
  • Fetal hematopoietic stem cell transplantation before 14th gestational week mainly for hemoglobinopathies and thalassemia
• Correction of Congenital heart disease

  • Prenatal surgery catheterization
  • Umbilical vessel catheterization and balloon valvuloplasty in utero for aortic or pulmonary astenosis
  • Monitoring and treatment in fetal arrhythmias (Digoxin, Propranolol etc)
• Surgical Fetal Therapy


  1. Anesthesia goal is safety of mother and fetus, prevention of maternal hypoxia and hypotension and maintenance of optimal uterine flow

  2. Procedures are generally performed in the second trimester, if possible, to avoid potential teratogenicity from the anesthetic agents

  3. Uterine incision tend to stimulate contraction which must be stopped with indomethacin, magnesium sulphate etc

  4. Intraoperative and postoperative monitoring of maternal: Myometrial contractions, intrauterine pressures, blood pressure, ECG, and pulse and blood gas levels

  5. Intraoperative and postoperative monitoring of fetal: Pulse oximetry (50-60% saturation), heart rate, blood gases, temperature and ECG

  6. Ultrasonographic monitoring in fetoscopic surgery
• Approaches to fetal surgery

  • Ultrasound guided in thoracoamniotic shunt placement in recurrent pleural effusion
  • Fetoscopic surgery in photocoagulation of communicating vessel in twin to twin transfusion. Usually under USS guidance. Also in amniotic band syndrome
  • Open surgery in myelomeningocoele between 24 and 30 weeks. Also in congenital diaphragmatic hernia by tracheal occlusion