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BIRTH DEFECTS AND 
PRENATAL DIAGNOSIS 
Marami binti Mustapa 
Anatomy Unit 
FMDH NDUM
Desired Learning Outcomes 
This lecture will enable you to: 
1. explain malformation, disruption & deformation 
2. explain...
Contents 
1. Causes of birth defect 
2. Types of birth defect 
3. Twin pregnancy 
4. Prenatal detection of birth defect
Birth defect 
• Terms used to describe structural, behavioral, functional, and metabolic 
disorders present at birth 
• Ma...
Causes of 2.7 million neonatal deaths in 193 
countries in 2010 
Source: Adapted from WHO. Born too soon. The global actio...
Birth defect 
• Minor anomalies occur in approximately 15% of newborns: 
• microtia (small ears) 
• pigmented spots 
• sho...
Types of abnormalities 
1. Malformations 
• Occur during organogenesis (3rd to 8th week of gestation) 
• Result in complet...
Types of abnormalities 
3. Deformations 
• Prolonged mechanical force to the growing fetus 
• Always involve musculoskelet...
Chromosomal and Genetic factors 
1. Chromosomal abnormalities 
• Numerical 
• Structural 
2. Gene mutations
Chromosomal abnormalities 
• Numerical/structural 
• 50% of spontaneous abortion is cause by major chromosomal 
abnormalit...
Chromosomal abnormalities 
Numerical abnormalities 
• Aneuploid is present of extra 
chromosomes (trisomy) or when one is ...
Trisomy 21 (Down syndrome) 
• Extra copy of chromosome 21 
• Mentally challenge, upward slanting eyes, 
small ears, cardia...
Trisomy 18 
• Mental retardation, congenital heart defects, low set ears, flexion of 
fingers and hands, renal anomalies, ...
Klinefelter syndrome 
• Occurs in male and detected at puberty 
• Features: small testes (lack of testosterone), 
gynecoma...
Turner syndrome 
• 45 X, 98% of fetus with this karyotype 
are spontaneously aborted 
• Features: short stature, premature...
Chromosomal and Genetic factors 
1. Chromosomal abnormalities 
• Numerical 
• Structural 
2. Gene mutations
Chromosomal abnormalities 
Structural abnormalities 
• Due to chromosome breakage 
caused by environmental factors 
(virus...
Structural abnormalities 
• Angelman syndrome 
• Deletion on long arm of chromosome 15 
• Mentally challenge, cannot speak...
Chromosomal and Genetic factors 
1. Chromosomal abnormalities 
• Numerical 
• Structural 
2. Gene mutations
Chromosomal and Genetic factors 
Gene mutations 
• Alter the functions of a normal 
gene 
• Mutations rate increased by a ...
Environmental factors 
1. Infectious agents 
2. Radiation 
3. Drugs 
4. Hormones 
5. Maternal diseases
Infectious agents 
1. Rubella (German measles) 
• Communicable disease 
• Features: cataracts, cardiac defects, deafness 
...
Infectious agents 
5. Toxoplasmosis 
• Maternal infection acquired by eating 
raw/poorly cooked meat containing 
toxoplasm...
Radiation 
• Ionizing radiation kills rapidly proliferating cells birth defect depending upon 
the dose and stage of devel...
Drugs 
Some can cause severe disruption of development, the effect vary 
1. Cigarette smoking 
• IUGR 
• Premature deliver...
4. Antibiotics 
Drugs 
• Tetracycline – tooth defects, diminished growth of long bones 
5. Anticoagulants 
• All except he...
7. Alcohol 
Drugs 
• Alcohol cause fetal alcohol syndrome (FAS) 
• FAS is a pattern of mental and physical birth defects t...
Hormones 
• Androgenic agents (synthetic progestins to prevent abortion) cause 
masculinization of the genitalia of female...
Maternal diseases 
Diabetes 
• Disturbances in carbohydrate metabolism during pregnancy in diabetic 
mothers 
• Causes a h...
Twinning 
• Risk of chromosomal anomalies are higher 
• Elevated risk congenital anomalies appears limited to same sex twi...
TWINS 
DIZYGOTIC 
2/3 
MONOZYGOTIC 
1/3 
Monochorionic monoamniotic <1% 
Monochorionic diamniotic -75% 
Dichorionic diamni...
Prenatal diagnosis 
• Growth and development of the fetus in vitro can be monitor using: 
• Ultrasound scan 
• Amniocentes...
Ultrasonography 
• Non-invasive 
• High frequency sound waves transmitted through the abdomen via a device 
called a trans...
Ultrasonography 
• Functions: 
• To confirm the gestational week of the fetus 
• To monitor the growth of the fetus: 
• Fe...
Maternal serum screening 
• Alpha fetoprotein (AFP) 
• Produce by fetal liver 
• Peeks at 14 weeks, increase in the matern...
Amniocentesis 
• To look for certain type of birth defect: 
• Down syndrome, neural tube defect 
• Needle is inserted into...
Chorionic villus sampling (CVS) 
• Indications: 
• To detect genetic abnormality of the fetus - Down syndrome 
• Maternal ...
Question 
The birth defects due to chromosomal abnormalities include 
A. Down syndrome. 
B. Fetal alcohol syndrome. 
C. Tu...
Birth defects and prenatal diagnosis
Birth defects and prenatal diagnosis
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Birth defects and prenatal diagnosis

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lecture notes on birth defects and prenatal diagnosis for medical students

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  • The world has seen many babies born with rare and bizarre birth defects, disorder or disease. These disorder were really shocking and disturbing around the world. Some are fairly well know while others are, thankfully, extremely rare. Let’s check out some of the strangest babies born with rare defect e.g. Chandre Oram, Frog Like Baby…http://bit.ly/2dtFe7Q
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Birth defects and prenatal diagnosis

  1. 1. BIRTH DEFECTS AND PRENATAL DIAGNOSIS Marami binti Mustapa Anatomy Unit FMDH NDUM
  2. 2. Desired Learning Outcomes This lecture will enable you to: 1. explain malformation, disruption & deformation 2. explain the common chromosomal & genetic causes of birth defect 3. list the common teratogens (environmental factors) for birth defect 4. list the common maternal factors causing the birth defect 5. explain / describe the common birth defects 6. explain the different types twin pregnancy 7. explain the common prenatal techniques to detect the fetal malformations
  3. 3. Contents 1. Causes of birth defect 2. Types of birth defect 3. Twin pregnancy 4. Prenatal detection of birth defect
  4. 4. Birth defect • Terms used to describe structural, behavioral, functional, and metabolic disorders present at birth • Major anomalies occur in 2 to 3% of liveborn infants, and an additional 2 to 3% in children by age 5 years • Birth defects cause 21% of infant deaths • The causes is unknown for 40% of persons with birth defects: • Genetic factors: chromosome abnormalities and mutant genes (15%) • Environmental factors (10%) • Combination of genetic and environmental influences (20 to 25%) • Twinning (0.5 to 1%)
  5. 5. Causes of 2.7 million neonatal deaths in 193 countries in 2010 Source: Adapted from WHO. Born too soon. The global action report on preterm birth. Geneva, World Health Organization, 2012
  6. 6. Birth defect • Minor anomalies occur in approximately 15% of newborns: • microtia (small ears) • pigmented spots • short palpebral fissures • Minor anomalies can be associated with major anomalies • Clue to detect major anomalies • Ear defect is a good indicator for major anomalies • Infants with 1 minor anomaly have a 3% chance of having a major malformation;2 minor anomalies have a 10% chance; 3 or more minor anomalies have a 20% chance
  7. 7. Types of abnormalities 1. Malformations • Occur during organogenesis (3rd to 8th week of gestation) • Result in complete/partial absence of a structure or in alterations of its normal configuration • Caused by environmental/genetic factors 2. Disruptions • Changes in the morphology of already form structures and due to destructive processes • E.g. bowel atresia due to vascular accident
  8. 8. Types of abnormalities 3. Deformations • Prolonged mechanical force to the growing fetus • Always involve musculoskeletal system • Can be treated/reversible
  9. 9. Chromosomal and Genetic factors 1. Chromosomal abnormalities • Numerical • Structural 2. Gene mutations
  10. 10. Chromosomal abnormalities • Numerical/structural • 50% of spontaneous abortion is cause by major chromosomal abnormalities • Causes 7% of major birth defects • Occur due to: late maternal age at the time of pregnancy (leads to chromosomal non-disjunction), radiation (causes chromosome deletions, translocations or breaks), viruses (German measles), chemical agents (anti-mitotic drugs)
  11. 11. Chromosomal abnormalities Numerical abnormalities • Aneuploid is present of extra chromosomes (trisomy) or when one is missing (monosomy) • Cause by nondisjunction resulting in individual with 47 chromosomes (trisomy) or 45 chromosomes (monosomy) • Nondisjunction increases with maternal age (> 35)
  12. 12. Trisomy 21 (Down syndrome) • Extra copy of chromosome 21 • Mentally challenge, upward slanting eyes, small ears, cardiac defects, hypotonia • Incidence increase with maternal age
  13. 13. Trisomy 18 • Mental retardation, congenital heart defects, low set ears, flexion of fingers and hands, renal anomalies, syndactyly, micrognathia (small jaw) • 85% lost during 10 weeks gestation to term, those born alive, die by 2 month of age
  14. 14. Klinefelter syndrome • Occurs in male and detected at puberty • Features: small testes (lack of testosterone), gynecomastia, micropenis, reduced facial and body hair, and infertility • Learning disabilities and delayed speech and language development • 1 in 500 to 1,000 newborn males • Extra copy of the X chromosome in each cell (47,XXY) • Cause by nondisjunction of XX homologues
  15. 15. Turner syndrome • 45 X, 98% of fetus with this karyotype are spontaneously aborted • Features: short stature, premature ovarian failure (ovaries develop normally at first, but oocytes usually die prematurely and most ovarian tissue degenerates before birth), webbed neck, lymphedema of the hands and feet, skeletal abnormalities, coarctation of the aorta • Have normal intelligence • 1 in 2,500 newborn girls worldwide
  16. 16. Chromosomal and Genetic factors 1. Chromosomal abnormalities • Numerical • Structural 2. Gene mutations
  17. 17. Chromosomal abnormalities Structural abnormalities • Due to chromosome breakage caused by environmental factors (viruses, radiation, and drugs) broken piece of a chromosome is lost abnormal infant • Cri-du-chat syndrome • partial deletion of the short arm of chromosome 5 • cat like cry, microcephaly, mentally challenge, widely set eyes, low-set ears, small jaw, rounded face and congenital heart disease
  18. 18. Structural abnormalities • Angelman syndrome • Deletion on long arm of chromosome 15 • Mentally challenge, cannot speak, exhibit poor motor development, and are prone to unprovoked and prolonged periods of laughter • Prader-Willi syndrome • If the defect is inherited on the paternal chromosome • Hypotonia, obesity, mentally challenge, hypogonadism, and cryptorchidism (no testes) a)Angelman syndrome b) Prader-Willi syndrome
  19. 19. Chromosomal and Genetic factors 1. Chromosomal abnormalities • Numerical • Structural 2. Gene mutations
  20. 20. Chromosomal and Genetic factors Gene mutations • Alter the functions of a normal gene • Mutations rate increased by a number of environmental agents (ionizing radiation) • E.g.: fragile X syndrome, achondroplasia, suprarenal hyperplasia
  21. 21. Environmental factors 1. Infectious agents 2. Radiation 3. Drugs 4. Hormones 5. Maternal diseases
  22. 22. Infectious agents 1. Rubella (German measles) • Communicable disease • Features: cataracts, cardiac defects, deafness 2. Cytomegalovirus (CMV) • Features: IUGR, microphthalmia, blindness, deafness, cerebral palsy, hepatosplenomegaly 3. Herpes simplex virus • Often occur during delivery • Features: cutaneous lesions, microcephaly, microphthalmia, retinal dysplasia 4. Varicella (chickenpox) • Before 20 weeks of gestation, causes skin scarring, muscle atrophy, hypoplasia of limbs, eye and brain damage 5. Human immunodeficiency virus (HIV) • Transmitted during delivery German measles Cutaneous lesion of HSV
  23. 23. Infectious agents 5. Toxoplasmosis • Maternal infection acquired by eating raw/poorly cooked meat containing toxoplasma cysts • Close contact with infected domestic animals (cats) or infected soil with animal faeces • Causes intracranial calcifications, chorioretinitis, hydrocephaly 6. Congenital syphilis • Congenital deafness, hydrocephalus, abnormal teeth and bones Intracranial calcifications
  24. 24. Radiation • Ionizing radiation kills rapidly proliferating cells birth defect depending upon the dose and stage of development of the conceptus at the time of exposure • Pregnant women at the time of the atomic bomb explosions over Hiroshima and Nagasaki: • 28% aborted;25% gave birth to children who died in their first year of life • 25% had severe birth defects involving the central nervous system • Radiation: mutagenic agent and can lead to genetic alterations of germ cells and subsequent malformations
  25. 25. Drugs Some can cause severe disruption of development, the effect vary 1. Cigarette smoking • IUGR • Premature delivery • Behavioral problems 2. Antinauseant and sleeping pill • Thalidomide: meromelia (limb reduction)/amelia (absent of limb/s) 3. Anticonvulsants • Trimethadione, phenytoin, valproic acid-teratogen • Causes: neural tube defects, craniofacial, heart, limb defects, eyelid ptosis Nick vujicic meromelia
  26. 26. 4. Antibiotics Drugs • Tetracycline – tooth defects, diminished growth of long bones 5. Anticoagulants • All except heparin are teratogenic – warfarin • Hypoplasia of nasal cartilage, CNS defects 6. Antineoplastic agents • It inhibit mitosis - highly teratogenic • Methotrexate – severe skeletal defects
  27. 27. 7. Alcohol Drugs • Alcohol cause fetal alcohol syndrome (FAS) • FAS is a pattern of mental and physical birth defects that is common in babies of mothers who drink heavily during pregnancy
  28. 28. Hormones • Androgenic agents (synthetic progestins to prevent abortion) cause masculinization of the genitalia of female fetus • Endocrine hormones as Diethylstilbestrol (DES) cause malformation of the uterus, uterine tubes, upper vagina, vaginal cancer and malformed testes of the baby
  29. 29. Maternal diseases Diabetes • Disturbances in carbohydrate metabolism during pregnancy in diabetic mothers • Causes a high incidence of stillbirths, neonatal deaths, abnormally large infants, and congenital malformations • Embryos use glucose as an energy source during gastrulation and neurulation: low blood glucose are teratogenic Phenylketonuria • Deficient in enzyme phenylalanine hydroxylase increased phenylalanine • High phenylalanine causes mental retardation, microcephaly, and cardiac defects
  30. 30. Twinning • Risk of chromosomal anomalies are higher • Elevated risk congenital anomalies appears limited to same sex twins and, hence, is probably related to monozygosity • Twins have about twice the risk of congenital abnormalities including neural tube defects (such as spina bifida), gastrointestinal, and heart abnormalities • Mother at the age of 32 has higher risk to get Down syndrome baby in multiple pregnancy in compare with singleton pregnancy (>35)
  31. 31. TWINS DIZYGOTIC 2/3 MONOZYGOTIC 1/3 Monochorionic monoamniotic <1% Monochorionic diamniotic -75% Dichorionic diamniotic -25% Dichorionic Diamniotic
  32. 32. Prenatal diagnosis • Growth and development of the fetus in vitro can be monitor using: • Ultrasound scan • Amniocentesis • Chorionic villus sampling • Maternal serum screening • To detect malformations, genetic abnormalities, placental or uterine abnormalities
  33. 33. Ultrasonography • Non-invasive • High frequency sound waves transmitted through the abdomen via a device called a transducer to look inside the abdomen • 2 approaches: • Transabdominal • Transvaginal • In Malaysia, at least 3 uss per pregnancy: 1st trimester, 2nd trimester and 3rd trimester • Use to manage pregnancy: • Reduced 60% mortality rate of low birth weight babies • Decide mode of delivery: SVD/LSCS
  34. 34. Ultrasonography • Functions: • To confirm the gestational week of the fetus • To monitor the growth of the fetus: • Femur length (FL) • Abdominal circumference (AC) • Biparietal diameter (BPD) • Crown-rump length (CRL) • To measure the amniotic fluid index • To determine the position of the placenta • To detect any abnormalities to the fetus or mother • Ovarian cyst • Oligohydramnios/polihydramnios • Down syndrome, anencephaly, spina bifida • Ectopic pregnancy
  35. 35. Maternal serum screening • Alpha fetoprotein (AFP) • Produce by fetal liver • Peeks at 14 weeks, increase in the maternal serum during 2nd trimester, begin a steady decline after 30 weeks of gestation • AFP increases in: • Neural tube defect, omphalocele, bladder exstrophy, amniotic band syndrome, sacrococcygeal teratoma, intestinal atresia • AFP decreases in: • Down syndrome, Trisomy 18, sex chromosomes abnormalities, triploidy • Decrease in human chorionic gonadotropin (hCG) and unconjugated estriol
  36. 36. Amniocentesis • To look for certain type of birth defect: • Down syndrome, neural tube defect • Needle is inserted into the amniotic cavity and 20 to 30 ml of amniotic fluid is withdrawn • Cultured amniotic fluid cells could be used to obtain fetal karyotype • Safe to be done between 15 to 18 weeks of gestation • Risk of miscarriage: 0.1%
  37. 37. Chorionic villus sampling (CVS) • Indications: • To detect genetic abnormality of the fetus - Down syndrome • Maternal age > 35 years old • History of neural tube defects in the family • Chromosome abnormalities in either parent • Mother who is x-linked disorder: haemophilia • Needle is inserted transabdominally/transvaginally into the placental mass 5 to 30 mg of villus tissue is aspirated • Done at 10-12 weeks of gestation • Complications: miscarriage less than 1%, leakage of amniotic fluid, uterine infection
  38. 38. Question The birth defects due to chromosomal abnormalities include A. Down syndrome. B. Fetal alcohol syndrome. C. Turner syndrome. D. Acquired immunodeficiency syndrome (AIDS). E. Klinefelter syndrome.

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