Teratogencity Types of birth defects :

Types of birth defects :

There are two main types of birth defects : structural and functional/developmental. However, the causes of about 70 percent of birth defects are unknown.Structural birth defects are related to a problem with body parts. Some physical problems include cleft lip or cleft palate, heart defects, such as missing or misshaped valves and abnormal limbs, such as a club foot. They also include neural tube defects, such as spina-bifida, problems that are related to the growth and development of the brain and spinal cord.Functional birth defects are related to a problem with how a body part or body system works. These problems often lead to developmental disabilities and can include things such as :Nervous system or brain problems – such as learning disabilities, intellectual and developmental disabilities, behavioral disorders, speech or language difficulties, convulsions and movement trouble. e.g. : Autism, Down syndrome, Prader-Willi syndrome and Fragile X syndrome.

Genetic birth defects have three main categories:

·      Single-gene defects

·      Chromosomal birth defects

·      Multifactorial birth defects

A)        Single-gene defects : A mutation (change) in a single gene can cause birth defects. e.g. dominant inheritance.  Each child of a parent with the gene has a 50-percent chance of inheriting the disorder. e.g. : Achondroplasia ,,Marfan syndrome. Other genetic diseases are inherited when both parents (who do not have the disease) carry an abnormality in the same gene and pass it on to a child. This is called recessive inheritance. Each child of two parents who have the abnormal gene has a 25-percent chance of inheriting the disorder. e.g : Tay-Sachs disease, Cystic fibrosis.

B)X-linked : e.g. : Hemophilia, Duchenne muscular dystrophy. C) Chromosomal birth defects : Abnormalities in the number or structure of chromosomes can cause many birth defects. e.g. : Down’s syndrome (Trisomy 21 or other rearrangements resulting in extra genetic material from this chromosome).Trisomy 18 and 13. Affected babies have multiple birth defects and often in the first months of life.Sex chromosome abnormalities (missing or extra copies of the sex chromosomes, X and Y). e.g. : Turner syndrome, Klinefelter syndrome.Multifactorial birth defects may be due to a combination of genes and environmental exposures. This is called multifactorial inheritance. In some cases, an individual may inherit one or more genes that make him more likely to have a birth defect if she is exposed to certain environmental substances, such as cigarette smoke. But if there is no exposure to the environmental substance before birth, she probably won’t have the birth defect. E.g. Cleft lip / palate, Neural tube defects (NTDs) spina-bifida and anencephaly and Heart defect.Environmental substance that can cause birth defects are called teratogens. These include alcohol, certain drugs/medications, infections and certain chemicals.

Alcohol : Each year between 1,000 and 6,000 babies in the Untied States are born with fetal alcohol syndrome (FAS) . This is pattern of mental and physical birth defects that is common in babies of mothers who drink heavily during pregnancy. Even moderate or light drinking during pregnancy may harm the baby

Drugs : Illegal drugs, including cocaine, marijuana and Ecstasy, may cause birth defects and must be stopped if a women contemplates a pregnancy, medical help may be required to help her.Infections : Certain infections can cause birth defects when a woman gets them during pregnancy. About 30,000 babies a year (about 1 in 150 newborns) in the US are born with a viral infection called cytomegalovirus (CMV) (6). About 8,000 infected babies each year develop permanent disabilities, including mental retardation and loss of vision and hearing (6). Pregnant women often get CMV from young children who have few or no symptoms.Sexually transmitted infections (STIs) : Untreated syphilis can cause stillbirth, newborn death or bone defects

Many metabolic disorders can be routinely detected with newborn screening tests, allowing early treatment and healthy development.e.g : Phenylketonuria (PKU) : Affected babies can have brain damage. Babies who have phenylketounria are placed on a special diet that prevents mental retardation. Affected individuals generally should follow a special diet throughout life.Galactosemia : Affected babies cannot process galactose which builds up and can lead to mental retardation, blindness and death. Affected individuals are treated with a special diet free of dairy products.Some metabolic disorders cannot yet be treated. An example is Tay-Sachs disease. Affected babies may have blindness, paralysis and death by age 5.Screening tests (blood tests) should be performed to see if there is increased risk of certain birth defects, including Down syndrome and spina bifida. These screening tests do not diagnose a condition, but suggest that further diagnostic testing is needed.

A genetic counseling should be given to the couple who have baby with a birth defect or who have a family history of birth defects. Genetic counselors can provide referrals to medical experts as well as to appropriate support in the community. Genetic counseling is available at most large medical centers and teaching hospitals. An estimated prevalence of 495,000 infants are born with congenital malformations every year. (2) In addition, 21,400 with Down’s syndrome, 9,000 with thalassaemia, 5200 with sickle cell anaemia, 390,000 with G6PD deficiency and 9760 with amino acid disorders are born every year.

Definition of a birth defect / congenital anomaly :A birth defect is defined as any abnormality affection body structure or function that is present from birth. It may be clinically obvious at birth or may be diagnosed only later in life. For example, spina bifida is a structural birth defect clinically obvious at birth and haemophilia is a functional birth defect that may present clinically only in infancy or childhood. A few birth defects, like Huntington disease, manifest in adulthood. Serious birth defects are life-threatening or have the potential to cause lifelong disability. (5) A birth defect is also called  a congenital disorder. More than 4,000 different birth defects are known, ranging from mild to severe.Causes of birth defects :-There are 3 major categories of causes Genetic (2) Environmental and (3) Complex genetic / unknown

Genetic causes : Chromosomal or single-gene disorders are known to account for about 25 - 30% of all birth defects. Chromosomal abnormalities are seen in about 0.5% of live births. Recently, use of ‘telomeric probes’ has increased this incidence further as about 5 – 7% of mentally challenged children have a cryptic translocation that connot be detected by traditional cytogenetic methods. A ‘mutation’ in the genetic locus can give rise of ‘signal gene disorder’. Not all mutant genes manifest at birth or lead to structural problems.Environmental causes : Account to 5 – 10% of causes of birth defects. These include nutritional deficiencies, maternal illnesses, teratogenic drugs or radiation and infectious agents. However, the extent of the damage depends  upon the timing of exposure and the individual’s genetic susceptibility. Complex Genetic / Unknown causes : These comprise of about 65 – 70% of birth defects. This may be caused by defects in more than one gene or a complex interaction of the environment and genes.

Identification of risk factors

Identification of these ‘risk factors’ should be a part of any prenatal care. The risk factors may be maternal or fetal. The common maternal risk factors include –

Advancing maternal age

However many younger mothers also have babies with chromosomal abnormalities and this is because more women below the age of 35 get pregnant than women over 35. The risk of maternal diabetes and hypertension is higher in older women, which in turn can cause growth problems in the babies.

Maternal diseases

Certain maternal diseases like Anti-phospholipid Syndrome, autoimmune diseases, renal diseases etc lead to fetal growth restriction and hence preterm delivery. Very early delivery is one of the leading causes of perinatal mortality and morbidity. Fetal growth restriction is known to lead to early adult-onset diseases like, Insulin-dependent diabetes, hypertension, hypertriglyceridemia etc, according to Barker’s Hypothesis.