Birth Defects and Prenatal

Diagnosis
By
AIAH LEBBIE
 Introduction
• Birth defect = congenital malformation =
congenital anomaly
• May be structural, behavioral, functional, and
metabolic disorders present at birth
• study of these disorders are is called
teratology or dysmorphology
 Classification
• Major structural anomalies occur in 2% to 3%
of liveborn infants
• additional 2% to 3% are recognized in children
by age 5 years accounting for a total of 4% to
6%
• Birth defects are the leading cause of infant
mortality, accounting for approximately 21%
of infant deaths
• They are the fifth leading cause of years of
potential life lost prior to age 65 and a major
contributor to disabilities
• They are also nondiscriminatory → mortality
rates are the same for all races
 Etiology of Major Birth Defects
• unknown = 40% to 60% of persons
• Genetic factors, such as chromosome
abnormalities and mutant genes = 15%;
• environmental factors produce = 10%
• combination of genetic and environmental
influences (multifactorial inheritance) = 20%
to 25%
• twinning = 0.5% to 1%.
• Minor anomalies occur in approximately 15%
of newborns
 microtia (small ears)
 pigmented spots
• Some in themselves detrimental to health
 some cases, are associated with major defects
 For example, infants with one minor anomaly
have a 3% chance of having a major
malformation
• two minor anomalies have a 10% chance; and
• three or more minor anomalies have a 20%
chance
• minor anomalies serve as clues for diagnosing
more serious underlying defects
• ear anomalies are easily recognizable
indicators of other defects and are observed in
virtually all children with syndromic
malformations
  
Types of Abnormalities

1. Malformations → partial or complete

absence of a structure or an alteration in the
configuration of the structure
– caused by environmental and/or genetic factors
acting independently or in concert
2. Disruptions result in morphological
alterations of already formed structures and
are due to destructive processes
 Examples → Atresia amniotic band effect
3. Deformations → mechanical forces that mold a
part of the fetus over a prolonged period
 Clubfeet → compression in the amniotic cavity
• A Syndrome →a group of anomalies occurring
together that have a specific common cause
– Diagnosis and risk of recurrence known
• An association → nonrandom appearance of
two or more anomalies that occur together
more frequently than by chance alone
• Cause → unknwn eg VACTERL association
 Principles of Teratology
• Refer to factors determining the capacity of an
agent to produce birth defects
I. genotype of the conceptus and how this
genetic composition interacts with the
environment
- maternal genome is also important → drug
metabolism and resistance to infection
II. Susceptibility to teratogens → developmental
stage and timing to exposure
III. dose and duration of exposure to a teratogen.
 Environmental Factors
Infectious agents
Rubella virus Cataracts, glaucoma, heart defects,
deafness, tooth abnormalities

Cytomegalovirus Microcephaly, blindness, mental

retardation, fetal death

Herpes simplex Microphthalmia, microcephaly, retinal

virus dysplasia

Varicella virus Limb hypoplasia, mental retardation,

muscle atrophy

HIV Microcephaly, growth retardation

Toxoplasmosis Hydrocephalus, cerebral calcifications,
microphthalmia

Syphilis Mental retardation, deafness

Physical agents

X-rays Microcephaly, spina bifida, cleft palate,

limb defects

Hyperthermia Anencephaly, spina bifida, mental

retardation, facial defects, cardiac
abnormalities, omphalocele, limb defects
Aminopterin Anencephaly, hydrocephaly,
cleft lip and palate
Diphenylhydantoin (phenytoin) Fetal hydantoin syndrome:
facial defects, mental
retardation
Valproic acid Neural tube defects, heart,
craniofacial, and limb
anomalies
Trimethadione Cleft palate, heart defects,
urogenital and skeletal
abnormalities
Lithium Heart malformations

Amphetamines Cleft lip and palate, heart

defects
Hormones

Androgenic agents Masculinization of female genitalia:

(ethisterone, fused labia, clitoral hypertrophy
norethisterone)
Diethylstilbestrol Malformation of the uterus, uterine tubes,
(DES) and upper vagina; vaginal cancer;
malformed testes
Maternal diabetes Variety of malformations; heart and
neural tube defects most common

Maternal obesity Heart defects, omphalocele

Warfarin Chondrodysplasia, microcephaly

ACE inhibitorsa Growth retardation, fetal death

Cocaine Growth retardation, microcephaly,

behavioral abnormalities, gastroschisis

Isotretinoin (vitamin Vitamin A embryopathy: small,

A) abnormally shaped ears, mandibular
hypoplasia, cleft palate, heart defects
Industrial solvents Low birth weight, craniofacial and neural
tube defects

Organic mercury Neurological symptoms similar to those

of cerebral palsy
 Radiation
• Ionizing radiation kills rapidly proliferating
cells → potent teratogen
• produces virtually any type of birth defect
– Dose of radiation
• stage of development of the conceptus at the
time of exposure
• Radiation is mutagenic agent
• Among women survivors pregnant 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% gave birth to children who had severe
birth defects involving the cns
 Cigarette smoking
• has not been linked to major birth defects
• contribute to intrauterine growth retardation
and premature delivery
Fetal alcohol syndrome
• indistinct philtrum
• thin upper lip
• depressed nasal
bridge,
• short nose
• flat midface
 Hormones
• Androgenic agents → synthetic progestins
(ethisterone and norethisterone )
– used during pregnancy to prevent abortion
– androgenic activity → masculinization of the genitalia in
female embryo The abnormalities
– enlarged clitoris associated with varying degrees of
fusion of the labioscrotal folds
• Endocrine disrupters → exogenous agents that
interfere with the normal regulatory actions of
hormones controlling developmental processes
– Diethylstilbestrol → developmental abnormalities
of the central nervous system and reproductive
tract
• raised the incidence of carcinomas of the vagina and
cervix
 Maternal Disease
• Diabeties → high incidence of
– Stillbirths
– neonatal deaths
– abnormally large infants
– Congenital malformations = 3-4 times non-diabetic
– severity and duration of the mother's disease
correlate with incidence of malformations
 Prevention of Birth Defects
• supplementation of salt or water with iodine
– eliminates mental retardation and bone deformities
resulting from cretinism
• strict metabolic control of diabetes prior to
conception reduces the incidence of birth defects
in their offspring
• Folate supplementation lowers the incidence of
– neural tube defects → spina bifida and anencephaly,
– reduces the risk of hyperthermia-induced
abnormalities
• A common denominator for all prevention
strategies is to initiate interventions prior to
conception
• It is important for physicians prescribing drugs
to women of childbearing age to consider the
possibility of pregnancy and the potential
teratogenicity of the compounds
 Prenatal Diagnosis
Modality Uses
Ultrasound fetal age
fetal growth
presence or absence of cong anomalies
Status of the uterine environment,
including the amount of amniotic fluid
placental position
umbilical blood flow
multiple gestations are present
Congenital - neural tube defects anencephaly and
malformations spina bifida
that can be - abdominal wall defects, such as
omphalocele and gastroschisis
determined by - heart defect
ultrasound - facial defets, including cleft lip and
palate
Maternal serum a-fetoprotein (AFP) is increased in
-- neural tube defects
Serum -omphalocele,
Screening -Gastroschisis
-bladder exstrophy,
-amniotic band syndrome
-sacrococcygeal teratoma,
- intestinal atresia
 AFP concentrations decrease in
-Down syndrome,
-trisomy 18,
-sex chromosome abnormalities
-triploidy

hCG and Levels decreased in

unconjugate -Down syndrome,
-trisomy 18,
d estriol -sex chromosome abnormalities
-triploidy
AFP
acetylcholineste
rase
fetal cells
sloughed into used for metaphase karyotyping and other
the amniotic genetic analyses → chromosomal abns
fluid, like translocations, deletions, trisomies etc

Chorionic Villus -advanced maternal age (35 ≥ years)

Sampling - family history of a genetic problem
- the presence of maternal disease, such as
diabetes
-an abnormal ultrasound or serum
screening