Embryology - Birth defects - Prenatal Diagnosis - Teratology - prevention of birth defects

1. Birth Defects &
Prenatal Diagnosis
Omar Nouri
MBBS, Ibn Sena University

2. Intended Learning Outcomes
At the end of this session you will be able to:
1. Describe malformation, disruption and deformation
2. Recognize principles of teratology
3. Identify common teratogens for birth defects
4. Identify common maternal factors causing birth defects
5. Describe prenatal techniques to detect and prevent birth defects
6. Review fetal therapy

3. Table of Contents

4. Introduction
Birth defect, congenital malformation &
congenital anomaly are terms used to
describe structural, behavioral, functional and
metabolic disorders present at birth.
Study of these disorders are known as
teratology / dysmorphology.

5. ● Major structural anomalies occur in approximately 3% of live born infants
● Birth defects accounts for approximately 25% of infant deaths and major
contributor to disabilities
● They are nondiscriminatory
● Minor anomalies occur in approximately 15% of newborns
○ They are not detrimental to health but may be associated with major defects.
○ They serve as clues for diagnosis of more serious underlying defects.
■ One anomaly = 3%
■ Two anomalies = 10%
■ Three or more = 20%

6. What causes birth defects?

8. Causes Birth Defects?

9. Types Of Abnormalities
MALFORMATIONS
● Occur during organogenesis (3rd to 8th week of gestation)
● Cause partial or complete absence of a structure or alters its
normal configuration
● Caused by enviromental or genetic factors
● E.g cleft lip and cleft palate

10. DISRUPTIONS
● Result in morphological alterations of already formed structures
● Due to destructive processes
● E.g. amniotic bands wrapped around structures causing vascular accidents
with digital amputations

11. DEFORMATIONS
● Results from mechanical forces that mold a part of the fetus over a prolonged
period, often involves musculoskeletal and usually are reversible.
● E.g. club feet due to oligohydramnios

12. Whoa!
Most critical period for birth defects and why ?

13. ● Beginning of third week until the end of eighth week
○ Period of organogenesis
● Teratogenic insults prior to the third week follow all or none rule
○ Embryo die or aborted
○ Growth was slowed but recovered
● After 8th week until birth = structural defects do not often occur
● Brain remains sensitive in this period
● NO TIME IN GESTATION IS SAFE FROM INSULTS BY TERATOGENS

15. Principles Of Teratology
Susceptibility to teratogenesis depends on:
1. Maternal and fetal genotype
2. Developmental stage at the time of exposure
3. Dose and duration of exposure to teratogen
Teratogens act in specific ways on developing cells to initiate abnormal embryogenesis.
E.g. inhibition of biochemical/molecular process, cell death, decreased cell proliferation

16. Enviromental Factors
● Infectious agents
● Radiation
● Drugs
● Hormones
● Maternal diseases

17. Infectious Agents
● Rubella (German Measles)
○ Congenital rubella syndrome
○ Causes:
■ Deafness
■ PDA
■ Congenital cataracts
■ Hepatosplenomegaly
■ Low birth weight

18. Toxoplasmosis
● Maternal Parasitic infection acquired by eating
raw/poorly cooked meat containing toxoplasma
cyst.
● Causes:
○ Intracranial calcification
○ Chorioretinitis
○ Hydrocephalus

19. Cytomegalovirus

20. Zika Virus

21. Radiation
● Ionizing radiations kills rapidly proliferating cells
● Produce any type of birth defect
● Depending on dose and stage of development during exposure
● Radiation is a mutagenic agent and can lead to genetic alterations of germ cells.

22. Teratogenic Drugs ?

23. Drugs
❖ THALIDOMIDE
➢ Anti-nauseant & aids sleeping. Prescribed for morning sickness
➢ Causes amelia and meromelia (total/partial absence of extremities)
❖ ANTICONVULSANTS
➢ Carbamazepine, Phenytoin, Valproic acid
➢ High risk of neural tube defects (spina bifida), heart and limbs.
❖ Antipsychotics, antidepressants & anticoagulant warfarin

25. Illicit Drugs, Alcohol & Cigarette
● COCAINE
○ Premature labour, IUGR, spontaneous abortion
● CIGARETTE SMOKING
○ Increases risk of orofacial clefts and heart defects
● ALCOHOL
○ Causes Fetal Alcohol Syndrome
○ Leading cause of intellectual disability

26. Hormones
● Androgenic agents (synthetic progestins to prevent abortion)
○ Cause masculinization of the genitalia of the female fetus
● Endocrine hormones (diethylstilbestrol)
○ Nonsteroidal form of estrogen
○ Well known teratogen and carcinogen
○ Causes malformation of the uterus, uterine tubes, upper
vagina, vaginal cancer and malformed testes of the baby

27. Maternal Disease
DIABETES
● High incidence of stillbirths, neonatal deaths, large infants, neural tube defects and
heart defects.

28. PHENYLKETONURIA
● Inherited disorder
● Deficiency of phenylalanine hydroxylase enzyme
● Results in high serum concentration of phenylalanine
● High risk of having infants with:
○ Intellectual disability
○ Microcephaly
○ Cardiac defects

29. How can we prevent/reduce the risk of birth defects?

30. Prevention Of Birth Defects
● Essential component of all prevention strategies is to initiate interventions prior to conception
● Physicians prescribing medications to women of childbearing age should consider the possibility
of pregnancy and potential teratogenicity
● Place women with DM/PKU under strict metabolic control prior conception.
● Folate supplementation lowers risk of neural tube defects
● Avoidance of alcohol during all stages of pregnancy

32. Methods to diagnose & prevent birth defects prenatal?

33. Prenatal Diagnosis
Methods to assess growth a development of the fetus in vetro
● Ultrasound (US)
● Maternal serum screening
● Amniocentesis
● Chorionic Villus sampling (CVS)
These techniques are designed to detect:
● Malformations
● Genetic abnormalities
● Overall fetal growth
● Complications of pregnancy, placenta and uterus abnormalities

34. Goal Of Prenatal
Diagnosis
Provide women who are at risk with information that
gives them the opportunity to make informed choices
about their pregnancy.

35. Factors Of High Risk Pregnancy
● Advanced maternal age ( above 35 )
● Family history of genetic problems and birth defects (neural tube)
● Presence of maternal disease
● Abnormal ultrasound or serum screening

36. Ultrasonography
● Noninvasive, safe and commonly used
● Use high frequency sound waves reflected from tissues to create images
● Approach is transabdominal / transvaginal (higher resolution images)
● Parameters revealed:
○ Fetal age and growth ( Crown-rump length during 5-10 weeks of
gestation)
○ Presence or absence of congenital anomalies
○ Status of uterine environment ( amniotic fluid)
○ Placenta position and umbilical blood flow

38. Maternal Serum Screening
ALPHA FETOPROTEIN (AFP)
● Produced by fetal liver
● Peaks at 14 weeks of gestation & leaks into the maternal circulation via the placenta (MSAFP)
● Levels increase in amniotic fluid & maternal serum in cases of several birth defects
● Levels decrease in down syndrome, trisomy18 and sex chromose abnomalities
AFP combined with 2nd trimester markers increase the detection rate for birth defects
Serum studies are not definitive for diagnosis, positive results require confirmation by invasive
techniques.

39. Amniocentesis
● Needle is inserted transabdominally into
the amniotic cavity guided by ultrasound
and fluid is withdrawn
● Fluid analyzed for AFP
● Fetal cells in the fluid can be used for
genetic analyses and chromosomal
abnormalities can be detected.

40. Chorionic Villus Sampling
● Needle is inserted transabdominally/transvaginally into the placental mass and
aspiring villus tissue
● Carries a risk of miscarraige, leakage of amniotic fluid and uterine infection
● There is indications of increased risk for limb reduction defects (digits)

41. Cordocentesis /Percutaneous Umbilical Blood Sampling
● PUBS is preferred method for obtaining fetal blood
● Ultrasound guided the needle is inserted into the
umbilical cord
● Used for diagnosis of hematological diseases
● Have a higher incidence of fetal loss than
amniocentesis

42. Fetal Therapy
● Fetal Transfusion (US guided into the umbilical vein)
● Fetal medical treatment (Administered to mother / directly to fetus IM inj. or via umbilical
vein)
○ Infections
○ Cardiac arrhythmias
○ Compromised thyroid functions
● Fetal Surgery
○ Open Surgery ( repair neural tube defects / heart abnormalities) between weeks 18-30
○ Fetoscopy ( places shunts in cases of urinary tract obstruction to relive problems
caused by amniotic bands)

45. Summary
● Various agents and genetic factors are known to cause congenital malformations
● Effect of teratogens depend on:
○ Maternal and fetal genotype
○ Stage of development at time of exposure
○ Dose and duration of exposure
● Most critical time ( Teratogenic period ) during the period of embryogenesis
● Prevention of birth defects is possible but depends on beginning preventive measure
before conception
● Techniques available to assess growth and development

46. “Not every birth defect is associated
with something we can do to prevent
it. But those we can prevent, we
should.”
—Dr. Hema DaSilva

47. References
● T.W Sadler (2019). Langman's Medical Embryology.
● Gary Schoenwolf(2020). Larsen’s Human Embryology.