Prenatal diagnosis Dr Hiba Ahmed Suhail M. B. Ch. B. /F. I. B. O. G Prenatal diagnosis Dr Hiba Ahmed Suhail M.B. Ch. B./F.I.B.O.G. College of medicine University of Mosul

Prenatal diagnosis: Prenatal diagnosis is the identification of a disease prior to birth. The early prenatal diagnosis and detection of congenital abnormality allows both parent and medical cares to plan the management for the pregnancy as: Reassurance of the parent Termination of pregnancy when the anomaly is incompatible with life . The time ,mode and place of delivery prepared to ensure good prognosis of the neonate . Offer in utero treatment.

Congenital anomaly refer to fetal alformation or disorders conferred by birth (born with ) Incidence 2-3 per 100 pregnancies The prenatal detection of the congenital abnormality is one of the aims of the routine antenatal care

Classification of common congenital abnormalities Structural abnormalities congenital heart disease Neural tube defects Cleft lipand palate Clubbed foot Chromosomal abnormalities trisomy 21(Downs syndrome) ,trisomy 13 and 18 Monosomy X(Turners syndrone ) Genetic Cystic fibrosis Sickle cell anaemia Thalassemia Miscellaneous viral infection

Test for fetal anomaly Screening is performed in all women in order to identify women who are at high risk of a disorder. They do not confer any risk to the pregnancy and are performed for disorders which there are accurate prenatal diagnostic tests. Diagnostic tests are carried out on pregnancies that have been identified as high risk by a prior screening test. It is usually invasive with risk of miscarriage .

Difference between prenatal screening and diagnostic tests Women at high risk All women Population tested To diagnose abnormality To Select a high risk group Purpose of test Ultrasound Amniocentesis Chorionic villous sampling cordocentesis Maternal history Maternal biochemistry Maternal virology Usual method of testing Patient aware of potential risks Diagnostic test should be available Prerequisite to test Small risk of miscarriage from invasive test Anxiety of a screen positive result Risk of test

Prenatal diagnostic tests can be divided into: 1-non-invasive tests ultrasound scanning  maternal blood sampling 2- invasive tests  Amniocentesis  chronic villus sampling and placental biopsy  Fetal blood sampling  Fetoscopy

1-Non invasive prenatal diagnosis Ultrasound scan At boking (11-14 weeks) Anomaly scan at 18-22 weeks Maternal serum tests Free fetal DNA can be extracted from maternal blood to determine fetal blood group in cases of alloimmunization , or to determine the sex of the fetus in X- linked disorders. Other studies 3 dimensional ultrasound scan and fetal MRI this permit the increased resolution required for certain fetal malformation like cleft lip and palate.

2- Invasive prenatal diagnostic tests Cordocentesis Chorion villous sampling amniocentesis 20-40 10-40 15-40 Gestation (weeks) Transabdominal Trans abdominal / trans cervical Route Fetal white blood cells Trophoblast cells Fetal fibroblast Cells sampled 1 Procedure related risk of miscarriage (%) Not needed 24-48 hours FISH for chromosomes 13, 18, 21 and XY, 24-48 hours Direct karyotype result 1-2 weeks 2-3 weeks Culture karyotype result None 1% Mosaicism rate on karyotype

Structural anomaly (Neural tube defects) Are most common major abnormalities . It occurs due to defect in formation of neurl tube defects during embryogebrsis. The aetiology is multi - factorial ( envirumental , genetic , pharmacological and geographical factors implicated. Anencephaly ( lethal ) , encephalocele ( prognosis related to size of defects ) Spina bifida usually affect spinal cord at the caudal level. The local effects (paralysis of legs, urinary and fecal incontinence ) depend on spinal levels and the number of spinal segments affected in the lesion. When a parent or previous sibling has had an NTD, the risk of recurrence is 5-10%.

Screening test Ultrasound 1- in first trimester can diagnose anencephaly , encephalocele. 2- At 20 weeks anomaly scan for spina bifda and hydrocephalous. Mid trimester maternal serum alpha - fetoprotein ( AFP ) levels are increased in pregnancies affected by open NTDs. Diagnostic test In the past, in case of screen positive women, they referred for amniocentesis to detect the presence of acetylcholinestrase in the amniotic fluid.

Prevention of neural tube defects: Periconceptional folate supplementation to the mother reduce risk folic acid should be given for at least 3 months prior to conceptionand for the first trimester of pregnancy. The dosage is 400 mcg for primary prevention and 4 mg for prevention of NTD in : Women with previously affected baby with NTD with type 1 diabetes mellitus in mother use antiepileptic drugs multiple pregnancy mother with hemoglobinopathies .

Structural anomaly (Congenital heart disease) CHD Anomalies of the heart and majors arteries are common heterogeneous They range from asymptomatic to the lethal one or that required surgery Risk factor: When a previous sibling or father is affected by CHD Offspring of women with type 1 diabetes. Drugs like lithium Viral infection like rubella Chromosomal abnormality Can be detected by ultrasound at 20 weeks

Chromosomal abnormalities (Downs syndrome) Down's syndrome (trisomy 21 ) it is an abnormal female gametogenesis either due to: Non dysjunction in meiosis (90 %) Un balanced translocation (6 %) Mosaism (4%)

Screening Diagnostic test Maternal age and history Increase risk with advanced maternal age. Age over 35 years old 1:750 , previous history of Down's 1:100 these should offer prenatal diagnosis. 2. Maternal serum biochemistry This iclude first trimester test of maternal serum HCG , estriol , inhibin ,PAPP-A , together with second trimester alpha feto protien (all are reduce except HCG) 3-Ultrasound for nuchal translucency Measurement of subcutaneous collection of fluid in nuchal (behind neck) region of fetus at 10-13 weeks gestation, it increase in affected fetus Diagnostic test Women with positive screening test are offered invasive tests (Amniocentesis and chorionic villus sampling ) .

Genetics disorders (hemoglobinopathies ) Sickle cell anaemia and thalassaaemia are both autosomal recessive with a risk of 25% affection of the offsbling Screening of at high risk populations (african in sickle cell anaemia and Mediterranian in thalassaemia) is by maternal serum electrophoresis Prenatal diagnosis by any invasive test (amniocentesis , CVS ,cordocentesis ) to take fetal cell for DNA study .

Cerebral calcification Features of congenital infection Congenital infections parvovirus toxoplasmosis Cytomegalovirus Rubella Infected children Cat-litter Under-cooked meat Infected individuals Source Aplastic anaemia hydrops Microcephaly Ventriculomegaly Cerebral calcification Heart defects Growth restriction Hepatomegally Thrombocytopenia Mental retardation Cataracts Features of congenital infection