Prenatal Diagnosis

Prenatal diagnosis Methods US - Structural abnormalities visible eg CDH, NTD, Doesn’t detect all cases dep on position, dating etc. Cant detect chromosomal / genetic problems Serological - Looks for alpha FP in maternal blood to detect NTD (high) Can look for Downs (low aFP + raised hCG + low unconjugated oestriol) = triple test Nuchal translucency - In 1st trimester. Used as a factor for downs risk. Amniocentesis Performed from 16 weeks using 20-22 gauge spinal needle transabdominally Indications - Chromosome analysis, inborn errors of metabolism, DNA analysis, and later in pregnancy for assessment of rhesus disease. Karyotype available in 3 weeks Risks - after 15 weeks miscarriage risk = 1.0%. If earlier greater risk of respiratory distress and postural deformities. If later risk of preterm rupture of membranes, chorioamnionitis and preterm labour. Rhesus sensitization can occur so Kleihauer test fb anti-D if req CVS – The risk is dependent on gestational age. The earlier in pregnancy, the higher the risk of miscarriage (e.g. ~2% at 11 weeks and ~1% at 16 weeks). Additional risks include membrane rupture, infection, rhesus sensitization, and uterine trauma. CVS is rarely performed before 10 weeks because of the risk of limb defects. Results usually in 48 hrs Chromosomal / Genetic Abnormalities Downs Syndrome (T21) – see below Edwards Syndrome (T18) Incidence - 1/3000 live births, mostly non-dysjuction, incidence increases with maternal age Features - Miscarriage/fetal death, growth restriction, severe learning defects, cardiac defects, hypoplastic lungs, flexion deformities, clenched fists with overlapping fingers (Fig 18 - below) , rocker-bottom feet, exomphalos, choroids plexus cysts, urogenital abnormalities. Most die within a few months; less than 10% survive a year. Patau Syndrome (T13) 1/5000 Turners (XO) 1/3000, 60% pure, 15% mosaic, rest = deletions etc increased incidence with increasing paternal age, decreased with increasing maternal age can be cystic hygroma, oedema & cardiac defects XXX 1/1000, more if maternal <40yrs Klinefelters syndrome (XXY) 1/700-2000 XYY – 1/700, no assoc with maternal age CF – testing offered if parents known carriers/sufferers. Mostly delta F508 mutation Fragile X – possible severity can be assessed by CVS Huntington’s chorea – testing via CVS Tay-Sachs – if parents are known carriers Structural Abnormalities Congenital Heart disease – 5-8/1000, four chamber view & detailed view approx 60% detection Neural Tube Defects Types - Spina bifida (meningomyelocele, meningocele), anencephaly, encephalocele Incidence - 1/1000 in UK. Caused by a combination of genetic factors & lack of folic acid Prevention - No personal/FH of NTD - 400mcg of folic acid min two months preconception til end of 1st trimester. If previous/FH/taking folate antagonists (eg anticonvulsants) take 5mg of folic acid Detection - serum AFP offered at 16-18 weeks. ( <2.3-2.5 times the population = low risk of NTD. A raised value makes NTD more likely (for other causes see below). If raised AFP a detailed scan is undertaken Features Spina bifida . A fluid-filled sac often containing neural tissue and an underlying defect of the spinal arch. 94% are lumbosacral (Fig 2 above). The degree of handicap varies and can include lower limb paralysis, urinary and fecal incontinence, limb deformities, hip dislocations, urinary infections and hydrocephalus (70%). Anencephaly . Absence of the forebrain and skull vault, facial distortion (fig 6 below). It is incompatible with life. Encephalocele . Herniation of the meninges and brain through the skull (usually occipital) Exomphalos & Gastroschisis Cause - Failure of rotation and re-entry of gut into abdominal cavity during fetal development. – Diagnosis - Both are associated with elevated maternal serum AFP and are diagnosed by ultrasound Management - Termination (if there are other anomalies or an abnormal karyotype). Surgical closure ASAP after birth (may have to be a 2 stage procedure). Risk of hypothermia/dehydration. Exomphalos - Herniation of the abdominal viscera through a defect at the umbilicus. Usually the peritoneal covering is preserved and the umbilical cord is inserted on to the sac. Other congenital abnormalities are common (10-15% have cardiac, bowel and chromosomal). Karyotyping by placental biopsy or blood sampling is advisable as 30% have chromosomal abnormality (aneuploidy), Gastroschisis – some link with environmental toxins. Defect of the abdominal wall separate from the insertion of the umbilical cord. The abdominal viscera herniate and the peritoneal covering is lost. Usually an isolated defect Renal malformations – detect by renal size & blood flow, oligohydramnios, empty bladder Posterior urethral valves – oligohydramnios and renal Dysplasia Potters syndrome – bilateral renal agenesis (oligohydramnios, pulmonary hypoplasia, limb deformity) Diaphragmatic Hernia Incidence – 1/1500 Causes - Failure of fusion or muscularization of the anterior and posterior leaves of the diaphragm. Often associated with aneuploidy, multiple malformation syndromes and cardiac defects Diagnosis - US will normally demonstrate abdominal contents (liver or bowel) in the chest with displacement of the heart. Offer karyotyping and look for other anomalies Prognosis - The outcome is determined by the degree of pulmonary hypoplasia and the presence of other abnormalities. The overall survival rate is 70%. Congenital Infections Chlamydia – risk of miscarriage, from intercourse / contact with farm animals Listeria – risk of miscarriage, from soft cheese, farm animals Toxoplasma – risk of hydrocephalus, chorioretinitis, from cats, uncooked meats and unwashed fruit, consider TOP if 1o infection <20 weeks Rubella – risk of FGR, deafness, CHD, mental retardatio, cateracts, miscarriage, risk greater in early pregnancy, consider TOP if < 12 weeks Chicken Pox – risk of limb hypoplasia, skin scarring, FGR, eye & neurological abnormality & hydrops, give zoster immunoglobulin and acyclovir (for neonatal infection) CMV – risk of FGR, microcephaly, sensorineural deafness, CP, hydrops, exomphalos, 40% of fetuses affected Parvovirus – risk of Aplastic anaemia, hydrops, myocarditis & fetal loss. Consider intrauterine transfusion B haemolytic strep – assoc with preterm ROM, low infection rate but high mortality & morbidity. Downs Screening Incidence - 1/800 (overall), increases with increasing maternal age (1/2000 at 25, 1/30 at 45) Causes - 95% due to non-dysjunction, 2% translocation 14:21, 2% other translocation, 1% mosaicism Recurrence risk is low, unless translocation downs (4% of cases) Features – epicanthic folds, visual & hearing problems, learning difficulty (skills gap increases with age), cardiac defects (40%), bowel problems (duodenal atresia), leukaemia (1%), alzeihmers (33% in over 50s), reduced life expectancy Screening – Triple test – blood test at 15-21 weeks (* for double test) sensitivy = 65% HCG (elevated in DS) * AFP (lower in DS) * - produced in yolk sac & fetal liver, peaks at 30 weeks (also indicates NTDs) Oestriol (lower in DS) (Quadruple test also uses inhibin) NT – 11-14 weeks, superior to double/triple test Is thicker in DS fetus Only offered to older women (higher risk), diabetics and multiple pregnancies (triple test inaccurate) If risk is > 1/250 = considered high risk à diagnostics Diagnostic – Amniocentesis (from 16 weeks) or CVS (from 10/11 weeks) Raised serum AFP Wrong dates Intrauterine bleeding NTD Congenital nephrosis Sacrococcygeal teratoma Multiple pregnancy IUFD (very high) Abdominal wall defects Placental dysfunction Dermatology problems Counselling for Fetal anomaly General counselling points • • • • • • • • Setting and style are important - supportive and non-directive Illustrations + clear documentation in notes of discussion. Letters with a lay-description to the patient and copied to relevant health professionals Management by a lead professional Important to check understanding & explain follow up req. Get them to repeat back The options for most pregnancies are simple (continue with the pregnancy or terminate) If continuing the following need to be discussed o Plan for pregnancy: surveillance, therapy o Plan for delivery: place, timing, method o Plan after delivery: surveillance, therapy, PM The woman should have a clear plan as to what the next steps are and contact details should be given Counselling for Downs Screening • Stress that majority of babies are normal • Does the woman understand what DS is? If not explain it in simple lay-terms: • Emphasise that screening is intended to identify those women at greater risk • Emphasise that the majority of the women identified as being at greater risk will have normal babies • Explain the implications of ‘low' (does not mean ‘no risk') and ‘high' risk (does not mean that DS is inevitable) • Explain what the options would be if identified as at ‘high risk' (offer invasive test) • Explain what the next steps are (ie when the tests will be offered and make the necessary appointments Counselling for increased downs risk • Does the woman understand what DS is? If not explain it in simple lay-terms: • Explain what risk estimate means presenting the figures in different ways (1: 150 mean that 149:150 chance that the fetus does not have DS which is about 99.3% chance). It is not a diagnosis. • Explain what the options are (invasive test or not) • Next steps will depend on the option chosen Abnormality Found by Chance at ‘Routine’ 20 Week Scan • Emphasize what's normal • Explain in precise lay-terms what has been seen (eg stomach in chest alongside heart) • Explain that the woman needs to speak to ‘expert' in more detail • No more than general mention of the implications of the findings (to avoid not answering the inevitable questions at all (more tests will be necessary, main concerns relate to how this might affect the baby's breathing after birth, surgery may well be necessary after birth) Anomaly found • ‘What have you been told is the problem with the baby? • Proceed to a more detailed explanation of the abnormality in lay-terms • Explain the overall prognosis is good with over X% of these babies surviving • Explain the implications for pregnancy and its management. Most units have detailed guidelines for common abnormalities covering o Plan for pregnancy: fetal surveillance o Plan for delivery: place, timing and method o Plan after delivery: medical and surgical care • Questions are answered • Meet the paediatric team and visit the neonatal unit where the baby will be managed • Contact details are given • A letter is written explaining the above and copied to the GP (and referring obstetrician if relevant) • The next steps including appointment are agreed with encouragement of more questions