BIRTH DEFECTS AND PRENATAL DIAGNOSIS

Hamid Hussain
 Birth Defects
• Birth defect, congenital malformation, and
congenital anomaly are synonymous terms
used to describe structural, behavioral,
functional, and metabolic disorders present at
birth.
 Teratology and Dysmorphology
TERATOLOGY
• That division of embryology and pathology dealing with abnormal
development and congenital deformations.
Or
• Science that studies the origin, causes, and prevention of birth
defects.
DYSMORPHOLOGY
Study of the causes, prognoses, treatment and prevention of birth
defects. Usually, a dysmorphologist is a clinical geneticist in a
genetics department. or
The branch of clinical genetics concerned with the study of
structural defects, especially congenital malformations.
• Major structural anomalies occur in
approximately 3% of live born infants, and
birth defects are a leading cause of infant
mortality, accounting for approximately 25%
of infant deaths.
• They are the fifth leading cause of years of
possible life lost prior to age 65 and a major
contributor to disabilities.
 Aetiology of birth defects

• In 40% to 45% of persons with birth defects,

the cause is unknown.
 Some known causes of Birth defects

1. Genetic factors, such as chromosome abnormalities

and mutant genes, account for approximately 28%
2. Environmental factors produce approximately 3% to
4%
3. a combination of genetic and environmental
influences (multi-factorial inheritance) produces
20% to25%
4. Twinning causes 0.5% to 1%
 Minor anomalies serve
as clues for diagnosing more serious underlying
defects.

• Minor anomalies occur in approximately 15%

of newborns.
• These structural abnormalities, such as
microtia (small ears), pigmented spots, and
short Palpebral fissures, are not themselves
disadvantageous to health but, in some cases,
are associated with major defects.
• For example, infants with one minor anomaly
have a 3% chance of having a major
malformation
• those with two minor anomalies have a 10%
chance
• and those with three or more minor
anomalies have a 20% chance
 Types of Abnormalities
MALFORMATION: a deformity in the shape or
structure of a part, especially when congenital

DISRUPTION: a morphologic defect resulting

from the extrinsic breakdown of, or interference
with, a developmental process.

DEFORMATION: An alteration in shape or

structure of a previously normally formed part.
 Malformation
• Malformations occur during formation of
structures, for example, during organogenesis.
They may result in complete or partial absence
of a structure or in alterations of its normal
configuration.
• Malformations are caused by environmental
and/or genetic factors acting independently or
in concert. Most malformations have their origin
during the third to eighth weeks of gestation
 Disruption
• Disruptions result in morphological alterations
of already formed structures and are caused
by destructive processes.
• Vascular accidents leading to transverse limb
defects and defects produced by amniotic
bands are examples of destructive factors that
produce disruptions.
 Amniotic band

• An abnormal condition of fetal

development in which fibrous
bands of tissue develop out of the
amniotic sac. The bands encircle
and constrict parts of the baby's
body, interfering with normal
development and sometimes
causing congenital amputation.
 Deformation
• Deformations result from mechanical forces
that mold a part of the fetus over a prolonged
period. Clubfeet, for example, are caused by
compression in the amniotic cavity.

• Deformations often involve the

musculoskeletal system and may be reversible
postnatally.
 Syndrome

• A syndrome is a group of anomalies occurring

together that have a specific common cause.
• This term indicates that a diagnosis has been
made and that the risk of recurrence is known.
 Association

• In contrast, association is the non- random

appearance of two or more anomalies that
occur together more frequently than by
chance alone, but the cause has not been
determined.
• Although they do not constitute a diagnosis,
associations are important because recognition
of one or more of the components promotes
the search for others in the group.
 VACTERAL Association
• VACTERL association is a nonrandom association of birth
defects that affects multiple organ systems. The term VACTERL
is an acronym with each letter representing the first letter of
one of the more common findings seen in affected children:

(V) = Vertebral Abnormalities

(A) = Anal Atresia
(C) = Cardiac (Heart) Defects
(T) = Tracheal Anomalies Including Tracheoesophageal Fistula
(E) = Oesophageal Atresia
(R) = Renal (Kidney) And Radial Abnormalities
(L) = (Other) Limb Abnormalities
 Environmental Factors

• Until the early 1940s, it was assumed that

congenital defects were caused primarily by
hereditary factors. With the discovery by N.
Gregg that rubella (German measles) affecting
a mother during early pregnancy caused
abnormalities in the embryo, it suddenly
became evident that congenital
malformations in humans could also be
caused by environmental factors.
• In 1961, observations by W. Lenz linked limb
defects to the sedative thalidomide and made
it clear that drugs could also cross the
placenta and produce birth defects.
 Teratogens Associated With Human Malformations
TERATOGEN CONGENITAL MALFORMATIONS
INFECTIOUS AGENT
Rubella virus Cataracts, glaucoma, heart defects, hearing loss, tooth
abnormalities

Cytomegalovirus Microcephaly, visual impairment, intellectual disability,

fetal death

Herpes simplex virus Microphthalmia, microcephaly, retinal dysplasia

Varicella virus Skin scarring, limb hypoplasia, intellectual disability,

muscle atrophy

Syphilis Intellectual disability, hearing loss

Toxoplasmosis Hydrocephalus, cerebral calcifications, microphthalmia

• Cataract: Any opacity in the lens of the eye
that results blurred vision

• Glaucoma: increase intraocular pressure

• Spina bifida: a developmental defect in which

the new born baby has part of the spinal cord
and its covering exposed through a gap in the
back bone
 Physical Agents
TERATOGEN CONGENITAL
MALFORMATIONS

X-rays Microcephaly, spina bifida,

cleft palate, limb defects

Hyperthermia Anencephaly, spina bifida,

intellectual disability
 Chemical Agents
TERATOGENS CONGENITAL MALFORMATIONS

Thalidomide Limb defects, heart malformations

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

Amphetamines Cleft lip and palate, heart defects

Warfarin Skeletal abnormalities (nasal hypoplasia, stippled
epiphyses)
 Chemical Agents
ACE inhibitors Growth retardation, fetal death

Mycophenylate mofetil Cleft lip and palate, heart defects, microtia, microcephaly
Immunosupressent
Alcohol Fetal alcohol syndrome (FAS), short Palpebral fissures,
maxillary hypoplasia, heart defects, intellectual disability

Isotretinoin (vitamin A) Isotretinoin embryopathy: small, 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

Lead Growth retardation, neurological disorders

 Hormones
TERATOGENS CONGENITAL MALFORMATION

Androgenic agents Masculinisation of female genitalia: fused labia, clitoral

hypertrophy (ethisterone, norethisterone)

DES Malformation of the uterus, uterine tubes, and upper

vagina; vaginal cancer; malformed testes

Maternal diabetes Various malformations; heart and neural tube defects most
common

Maternal obesity Neural tube defects, heart defects, omphalocele

SSRIs, Selective serotonin reuptake inhibitors; ACE, angiotensin-converting enzyme;

DES, diethylstilbestrol.
 Prevention of birth defects
• Many birth defects can be prevented. For
example, supplementation of salt or water
supplies with iodine eliminates mental
retardation and bone deformities resulting
from cretinism.
 Metabolic control (A very good friend)

• Placing women with diabetes or PKU under

strict metabolic control prior to conception
reduces the incidence of birth defects in their
offspring.
 Protect the child by Folate

• Folate supplementation lowers the incidence

of neural tube defects, such as spina bifida
and anencephaly.
 Avoid Alcohol and drugs

• Avoidance of alcohol and other drugs during

all stages of pregnancy reduces the incidence
of birth defects.
 Timely Intervention

• A common denominator for all prevention

strategies is to initiate interventions prior to
conception.
• Such an approach also helps prevent low-
birth-weight babies.
 Medication should made by expert
Clinician
• 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.
• Recently hundreds of children have been born
with severe craniofacial, cardiac, and neural
tube defects produced by retinoids (vitamin A
embryopathy).
ALLAH brought you out of your mothers’ wombs in this
state that you knew nothing: HE gave you ears and eyes
and thinking minds so that you may be grateful.
Al-Nahl. Surah 16. Ayat 78. para 14