1. Prenatal screening / Diagnosis

2. Prenatal diagnosis or prenatal screening Test carried out to determine for presence of diseases or conditions in a fetus before it is born. INDICATIONS / AIMS FOR PRENATAL SCREENING A) To detect birth defects such as : Neural tube defects, Down syndrome chromosome abnormalities, Genetic diseases Other conditions, such as spina bifida, cleft palate, Tay Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, Muscular dystrophy, etc.

3. B) Screening can also be used for prenatal sex discernment. C) It has also been done to determine characteristics generally not considered birth defects in other words parents looking for “designer babies” D) In suspected cases of increased risk of a malformation, chromosome abnormality, or genetic disorder following a familial, maternal, or fetal condition. E) In abnormal maternal results such as ultrasound exams, maternal serum screening (Prenatal screening). F)Another important reason for prenatal screening/diagnosis is advanced maternal age usually 35 years or greater at the time of delivery.

4. AIMS/ OBJECTIVES OF PRENATAL DIAGNOSIS At the end of screening, there are 3 purposes for prenatal diagnosis: 1) To enable timely medical or surgical treatment of a condition before or after birth. 2) To give the parents the chance to abort a fetus with the diagnosed condition. 3) To give parents the chance to "prepare" medically, psychologically, socially and financially for a baby with a health problem or disability, or for the likelihood of a stillbirth. Armed with this information before birth means that healthcare staff as well as parents can better prepare themselves for the delivery of a child with a health problem.

5. Techniques for pathologic exam in prenatal screening/ diagnosis 1)Chromosome Analysis / Studies :  Useful in pregnancies where there is advanced maternal age.  A chromosome abnormality in a previous offspring, a parent, or a close relative.  A previous offspring with multiple malformations with no previous chromosomal study.  Fetal sex determination in pregnancies at risk of a serious X- linked disorder for which specific prenatal diagnostic tests are not available. A repeat testing should be considered in a child with a normal prenatal chromosome analysis but with signs of a possible chromosome abnormality.

6. Biochemical Studies Undertaken most often when a known abnormality is present in a family and can be diagnosed by a specific biochemical test. For diagnosis of many common inborn errors of metabolism can by testing for enzyme deficiency or an abnormal metabolite. In a few circumstances, biochemical testing may be used when there is no family hx of a disorder but prenatal ultrasonographic findings are suggestive of a biochemical disorder.

7. Molecular/ Genetic Studies When there is a positive family history of a specific genetic disease or prenatal findings point to a possible single-gene disorder that can be diagnosed by molecular techniques. The consultation of a geneticist, genetic counselor, or other clinician familiar with the utility of these prenatal tests may be particularly helpful.

8. Microbiologic Culture: They include cultures for anaerobic and aerobic bacteria, viruses, fungi. Used in diagnosis/ confirmation of congenital infections eg TORCH. Flow Cytometry: Determines amt of DNA in the fetus. However cannot give any information on individual chromosome with aneuploidy.

9. Methods for Prenatal Screening / Diagnosis The methods of testing can be invasive or non-invasive in nature. The non-invasive include: Ultrasonography : Ultrasonography has become the 1 0 method for fetal anatomic imaging. It may be used in pregnancy to monitor fetal growth, movement, position, and morphology; assess amniotic fluid volume; and establish gestational age and placental location. In the case of neural tube defects, a detailed ultrasound can non-invasively provide a definitive diagnosis.

10. MATERNAL SERUM SCREENING STUDIES (i.e AFP) MSAFP concs are increased in many abnormal fetal conditions including open NTDs and defects of the genitourinary and gastrointestinal systems. MSAFP screening results are abnormal in approximately 90% of cases of anencephaly and approximately 80% of cases of open spina bifida. Blood tests for select trisomies (Down syndrome in the United States, Down and Edwards syndromes in China) based on detecting fetal DNA present in maternal blood have become available. MRI MRI may be especially useful for the evaluation of fetal CNS abnormalities, when oligohydramnios is present, or when ultrasonography is difficult. MRI generally is not recommended during the first trimester.

11. Fetal Echocardiography Fetal echocardiography is usually performed after 20wks' gestation. Can identify a substantial number of major structural cardiac defects and rhythm disturbances when used with duplex and/or color-flow Doppler ultrasonography. It is considered when there is an increased risk of cong. heart dx b/cos: 1) there is an extracardiac malformation identified by ultrasonographic examination 2) There has been prenatal exposure to a teratogenic agent 3) There is a family history of congenital heart defects, especially in a parent or sibling;

12. 4) A fetal chromosome abnormality or genetic disease associated with heart defects is suspected 5) A maternal disease associated with fetal structural heart defects, such as diabetes or phenylketonuria, or maternal disease associated with fetal cardiac arrhythmia, such as lupus erythematosus, has been identified 6) A cardiac defect is suspected by findings on routine ultrasonography 7) A fetal arrhythmia has been detected on auscultation or examination.

13. Invasive Methods: If an elevated risk of chromosomal or genetic abnormality is indicated by a non-invasive screening test, a more invasive technique may be employed to gather more information. They include: Amniocentesis: Most commonly used to obtain fetal cells that can be analyzed for cytogenetic, biochemical, or molecular abnormalities. It involves probes or needles inserted into the uterus from 14 wks of gestation, up to about 20 wks. Indication for use It is offered to women at ages 35yrs and above because of the increased risk of aneuploidy (an abnormal number of chromosomes in the fetus). It is also used commonly to evaluate pregnancies in which an ultrasound exam or a maternal serum screening result has identified a possible fetal problem

14. Chorionic villus sampling:  Done earlier (between 9.5 and 12.5 weeks of gestation).  It may be slightly more risky to the fetus e.g Transcervical chorionic villus sampling carries a significantly higher risk, compared with a 2 nd trimester amniocentesis, of total pregnancy loss.  Cytogenetic, molecular, and some biochemical studies can be performed on CVS samples.  Women who have had CVS should also have maternal serum α-fetoprotein (MSAFP) screening at 15 to 20 wks' gestational age to screen for fetal NTDs.

15. Sampling of Fetal Blood In some circumstances, it may be useful to obtain a sample of fetal blood. This technique, referred to as cordocentesis or percutaneous umbilical blood sampling. May be used to assess fetal blood disorders, fetal infections, or isoimmunization or may be used for rapid fetal karyotyping. It also has been used to supply fetal treatment such as transfusions and drugs. Fetal loss or spontaneous abortion is reported in approximately 1% to 2% of cases, making the risk associated with this procedure higher than that with amniocentesis or CVS.

16. Indications for Invasive Diagnostic testing The following are some reasons why a patient might consider her risk of birth defects high enough to warrant skipping screening and going straight for invasive testing : Women over the age of 35 Women who have previously had premature babies or babies with a birth defect, especially heart or genetic problems.

17. Indications for Invasive/ Diagnostic testing Women who have family hx or ethnic backgrounds prone to genetic disorders, or whose partners have these. Women who are pregnant with multiples (twins or more). Women who have previously had miscarriages. Women who have high blood pressure, lupus, diabetes, asthma, or epilepsy

18. Typical screening sequence At 6 weeks of pregnancy, early ultrasound scan may be offered to help confirm the gestational age of the embryo and check whether it is a single or twin pregnancy. However, such a scan is unable detect common abnormalities. At wks 10-11, nuchal thickness scan (NT) may be offered which can be combined with blood tests, beta-hCG, a serum marker that correlate with chromosomal abnormalities, in what is called the First Trimester Combined Test. The results of the blood test are then combined with the NT, u/sound measurements, maternal age, and gestational age of the fetus to yield a risk score for Down Syndrome, Trisomy 18, and Trisomy 13. 1 st Trimester Combined Test has a sensitivity (i.e. detection rate for abnormalities) of 82-87% and a false-positive rate around 5%.

19. Ethical and practical issues The option to continue or abort a pregnancy is the 1 0 choice after most prenatal testing. Are the risks of prenatal diagnosis, such as amniocentesis worth the potential benefit? Knowing about certain birth defects such as spina bifida and teratoma before birth may give the option of fetal surgery during pregnancy, or assure that the appropriate treatment and/or surgery be provided immediately after birth. Questions of the value of mentally or physically disabled people in society. How to ensure that information about testing options is given in a non-directive and supportive way. That parents are well informed if they have to consider abortion vs. continuing a pregnancy.

20. Will the result of the test affect treatment of the fetus? In some genetic conditions, e.g cystic fibrosis an abnormality can only be detected if DNA is obtained from the fetus. Usually an invasive method is needed to do this if a genetic disease is detected, there is often no treatment that can help the fetus until it is born. However in the US, there are prenatal surgeries for spina bifida fetus. Early diagnosis gives the parents time to research and discuss post-natal treatment and care, or in some cases, abortion. Genetic counselors are usually called upon to help families make informed decisions regarding results of prenatal diagnosis. False positives and false negatives No prenatal test can detect all forms of birth defects and abnormalities.

21. Informed consent and medical malpractice Obstetricians have an ethical duty to properly inform patients of their options, specifically the availability of screening and diagnostic testing. Physicians have been successfully sued by women who gave birth to babies with abnormalities that could have been detected had they known about their screening options. Also, physicians who fail to inform their patients of the risks of amniocentesis and CVS might be found guilty of negligence informed consent in the event that the patient sues after a procedure-related miscarriage or fetal damage.

22. CONCLUSIONS Pediatricians may be called on to counsel a family in which prenatal diagnosis is being considered or in which there is a fetus with a genetic disorder. It is important that pediatricians involve themselves at a level appropriate to their training and experience, that they clarify their role in the prenatal diagnostic process with the family, and that they document their discussion and recommendations. More frequently, an obstetrician, clinical geneticist, and/or a genetic counselor will direct the diagnostic evaluation and provide pretest and posttest counseling.

23. Because of a previous relationship with the family, the pediatrician may be called on to review this information and assist the family in the decision-making process. The pediatrician should be familiar with the principles of prenatal genetic diagnosis and know how to apply them to specific problems in genetic counseling, diagnosis, and management in clinical practice.

24. Pediatricians should be familiar with resources available in their region for obtaining information about whether and how a specific disorder can be diagnosed and when and where to refer patients for prenatal genetic diagnosis. The technology of prenatal diagnosis is changing rapidly, and genetic consultants can assist pediatricians in the appropriate use and interpretation of the diagnostic tests that are available.