Download EMBRYOLOGY TERATOGENESIS LEARNING OBJECTIVE . At the

EMBRYOLOGY
TERATOGENESIS
LEARNING OBJECTIVE
. At the end of lecture student should be able to
 Define the birth defects
 Classify the birth defects
 Enumerate the causes of birth defects
 Know the genetic factor involve in birth defects
 Name the environmental causes producing birth defects .
 TERATOGEN
 A teratogen is any infectious agent,drug,chemical or
radiation that alters fetal morphology or fetal function if
the fetus is exposed during a critical stage of
development.
 THE RESISTANT PERIOD
 Week 1 of development.
 Is the time when the conceptus demonstrates
the
 ’all or none’ phenomenon
 THE MAXIMUM SUSCEPTIBILITY PERIOD
 Week 3 to 8 embryonic period.
 Is the time during which the embryo is most
susceptible to teratogens because all organs
morphogenesis occurs at this time.
 THE LOWER SUSCEPTIBILITY PERIOD
 Weeks 9 to 38 fetal period.
 Time during which the fetus has a lower susceptibility to
teratogens because all organs
systems have already formed.
 Teratogens expose generally results
in a functional derangement of an
organ system
 INFECTIOUS AGENTS
 May be viral or nonviral.
 Viral infections may reach the fetus
via the amniotic fluid after vaginal infection transplacentally
via the bloodstream after maternal viremia,or by direct
contact during passage through an infected birth canal
 Bacteria appears to be non teratogenic.
 RUBELLA VIRUS
 Transmitted to the fetus
transplacentally.
 Risk greatest during the first
month of pregnancy.
 Clinical menifestation.
 Fetal rubella infection results in
the classic triad of cardiac
defects(patent ductus
arteriosus,pulmonary artery















stenosis,arterioventricular septal defects),cataract,and
low birth weight.
The clinical manifestations include intrauterine growth
retardation,hepatosplenomegaly,generalized
adenopathy,Hemolytic
anemia,hepatitis,jaundice,meningoencephalitis,eye
involvement,osteitis,and sensorineural defects
CYTOMRGALO VIRUS
Most common fetal infection.
Transmitted to the fetus transplacentally or by the virus
ascending from the cervix during recurrence.
Transmitted to perinates during passage through the
birth canal or through breast milk.
Clinical manifestations are
Sensorineural deafness,intrauterine growth
retardation,microcephaly,chorioretinitis,hepatospleeno
megaly,osteitis,discrete cerebral
calcification,mental retardation,heart
block,bluish purple lesions on yellow
jaundice skin.
HERPES SIMPLEX
Transmitted to the fetus transplacentally
occasionally.
Most commonly transmitted to the fetus by
direct
contact during passage through an infected birth canal.
At 10 to 11days of age clinical manifestation.
Disease localized to skin,eye,mouth.
At 15 to 17days of age.
CNS involvement.
 Untreated disease results in an 80%
mortality rate and
 most survivors have neurologic sequele.
 The only intervention to prevent infection is delivery by
cesarean section with in 4 to 6hours of ruture of
amniotic membranes.
 VERICELLA ZOSTER
 Transmitted to the fetus transplacentally.
 Clinical manifestations of fetal varicella syndrome
include
 Cicatricial(scarring) skin,digit hypoplasia,limb paresis,limb
paralysis,hydrocephalus,mental
retardation,microcephaly,seizure,chorio
retinitis,
 and cataract.
 Treatment of the neonate is by
acyclovir.
 HUMAN IMMUNODEFICIENCY VIRUS
 HIV is transmitted to the fetus through
 blood containing HIV or HIV infected lymphoid cells near
 the time of delivery after 35days of gestation.
 HIV infection does not appear to cause any congenital
malformation but results in chronic mutisystem
infections.
 FUNGAL INFECTIONS
 BACTERIAL INFECTIONS.
 VIRAL INFECTIONS.
 NON VIRAL INFECTIONS
 TOXOPLASMA GONDI
 Transmitted to the fetus
 transplacentaly,
 if untreated
 results in miscarriage,perinatal
 death,chorioretinitis,microceph


















aly,
Hydrocephalus encephalomyelitis with
cerebral calcification.
Surviving infants are left with major neurological sequele(eg
mental retardation,seizure,spasticity,and visual dificits)
TREPONEMA PALLIDUM
Transmitted transplacentally.
Infection acquired at birth
through contact with genital lesion in the birth canal.
Results in miscarriage,perinatal
death,hepatospleenomegally,hepatitis
,joint swelling,vesiculobullous
blisters,nasal discharge with
rhinitis,maculopapular rash located in
extremities,,eye findings(
chorioretinitis,glaucoma,cataract and
uveitis),anemia,jaundice,focal
erosions of the proximal medial tibia,saw tooth appearance
of metaphysis of long bones,abnormal teeth,and acute
syphilic leptomeningitis that may present as neck
stiffness,and chronic meningovascular syphilis(cranial nerve
palsy,hydrocephalus,cerebral infarction)
TORCH INFECTIONS
Are caused by,
Toxoplasma.
Rubella.
Cytomegalovirus.
Herpes virus.
And other bacterial and viral infections that are grouped
together because they cause similar clinical and pathological
manifestations.
DRUGS
THALIDOMIDE
Prescribed for pregnanat women for morning sickness.
 Drug cause limb reduction,ear and nasal
abnormalities,cardiac defects,lung defects,pyloris
stenosis,gestrointestinal atresia.
 AMINOPTERIN
 Used in cancer chemotherapy.
 Causes small stature,abnormal cranial ossification,ocular
hypertelorism,low set ears,cleft palate,myelomeningocele.
 BUSULFAN
 Are alkylating agents used in chemotherapy.
 Cause cleft palate,eye defects,hydronephrosis,renal
agenesis,absence of toes,growth retardation.
 PHENYTOIN
 Antiepileptic drug.
 Causes growth retardation,mental
retardation,microcephaly,craniofacial defects,nail and digit
hypoplasia.
 TRIAZOLAM AND ESTAZOLAM
 Are hypnotic drugs.
 Causes cleft palate.
 WARFARIN
 Anticoagulant.
 Causes stippled epiphysis,mental
retardation,microcephaly,seizure,fetal hemorrhage,optic
atrophy in fetus.
 ISOTRETINOIN
 Used in the treatment of severe acne.
 Causes CNS abnormalities,external ear abnormalities,eye
abnormalities,facial dysmorphia,cleft palate.
 CLOMIPHENE

















Nonsteroid ovulatory stimulant used in women.
There are reports of birth anomalies.
DIETHYLSTILBESTROL
Used to prevent spontaneous abortion.
Causes hypoplastic uteruspremature labour,and cervical
incompetance.
ETHISTERONE,NORETHISTERONE,AND MEGESTROL
Causes masculinization of genitalia in female
embryo,hypospadias in males and cardiovascular
anomalies.
NORETHINDRONED AND LEVONORGESTROL
Are oral contraceptive.
Cause an increase of fetal abnormalities.
Particularly of VACTERL SYNDROME.
Consisting of
vertebral,anal,cardiac,tracheoesophageal,renal,and limb
malformation.
NICOTINE
Delivered to the fetus through cigarette smokiong.
Causes intrauterine growth retardation,premature
delivery,low birth weight,and fetal hypoxia.
ALCOHOL
Causes fetal alcohol syndrome,which results in mental
retardation,microcephaly,limb deformities,craniofacial
abnormalities,cardiovascular defects.
 OTHER DRUGS
 Tetracycline
 Streptomycin
 Phenobarbitol
 Valproic acid
 Diazepam.
 Lithium.
 Hidrochlorothiazide.








CHEMICAL AGENTS
Mercury.
Lead.
Polychlorinated biphenyls(PCBs)
Potassium iodide.
Bisphenol.
Phthalates.
Methoxychlor.





RECREATIONAL DRUGS
Lysergic acid(LSD) has not shown to be teratogenic
Marijuana has not shown to be teratogenic.
Caffeine has not shown to be teratogenic.
Cocaine results in an increased
risks of congenital
abnormalities,still births,low birth
weight,and placental abruption.
 Heroin has not shown to be teratogenic,it is the drugs
that are taken with heroin that produce congenital
anomalies.methadone used to replace heroin is not
teratogenic but is also associated with severe neonatal
withdrawal.
 IONIZING RADIATION
 ACUTE HIGH DOSE(over 250rads) of radiation results in
microcephaly,mental retardation,growth retardation,and
leukemia.
 AFTER EXPOSURE TO GREATER THAN 25rads classic
fetal defects will be observed so that termination of
pregnancy should be offered as an option.
 DIAGNOSTIC RADIATION.
 Radioactive iodine cocktails for organ visualization should be
avoided after 10 week of gestation because fetal thyroid
development can be impaired.
 REFERENCES.
 KEITH L.MOORE Developing Human 8th Edition chapter-20
pages 457-485.