The TORCH complex is a group of similar malformations induced by microbial teratogens. These organisms are Toxoplasma, Rubella, Cytomeglovirus, Herpes simplex virus and Others such as syphilis, etc. These microbes affect 1-5% of all live births and are among the leading causes of neonatal morbidity and mortality.
General symptoms include premature birth, growth retardation, neurological abnormalities, damage of the eye, liver, heart and ear as well as bone lesions. Microcephaly, hydrocephaly, seizures and psychomotor retardation accompany these malformations. Toxoplasma
| Toxoplasma gondii is a protozoan parasite which is able to cross the placenta. Fetal infection may result in hydrocephaly, microphthalmia, chorioretinitis, brain lesions and multiple organ damage and dysfunction. Twenty-five percent of reproductive age women have antibodies against toxoplasma yet fetal infection occurs only in 0.1% of all live births (approximately 1 in 4,000 pregnancies). | |
The severity of fetal damage directly relates to time of exposure to the teratogen. If a mother is infected in the first trimester, 15-20% of infected fetuses acquire severe manifestations. Second trimester maternal infection yields 25-30% of infected newborns with severe malformation. Third trimester infection results in 60% of infected newborns with severe malformation, 90% of which will be asymptomatic at birth.
Untreated maternal syphilis results in fetal infection 75-90% of the time. Several hundred children are born each year with syphilis; seventy-five percent of them are asymptomatic at birth.
Early infection most often results in spontaneous abortion. Some newborns do survive but are small for gestational age, anemic with spleen and liver malformations, have skin lesions and nasal discharge and bone and joint pain. Gestationally late infections often present in children over 2 years of age. They have nerve deafness, dental and bony abnormalities, cardiovascular defects and skin lesions.
In utero infection with rubella may result in glaucoma, microphthalmia, cataracts, cardiac malformation, hearing loss and mental retardation. Together, these malformations constitute congenital rubella syndrome.
Congenital rubella syndrome was the first evidence (published by Gregg in 1941) that the placental barrier between mother and fetus does not fully protect the fetus from teratogens. Gregg found that fetuses infected during their first trimester of gestation have a 1 in 6 chance of contracting eye cataracts, heart malformations, and deafness.
The rubella epidemic of 1963-1965 resulted in 1,800,000 infected individuals, approximately 20,000 fetal deaths and about 30,000 infants born with birth defects. In years without noticeable rubella outbreaks, these statistics fall to approximately 26 affected infants per 100,000 live births. Since the introduction of the rubella vaccine in 1969 there are less than 120 cases of congenital rubella syndrome reported each year.
There are two possible mechanisms of pathogenesis: direct viral effects or damage due to immune response. Infection with the virus stops cells from replicating; therefore, organogenesis is inhibited, causing malformations. Altered organogenesis will result in malformations of the eye and heart. An immune response may induce cell lysis, tissue destruction, the disruption of vascular walls and scarring due to inflammation. Tissue destruction leads to hearing loss, brain defects, cataracts and pulmonary artery stenosis.
Infection early in gestation with CMV is fatal while a late infection might lead to blindness, deafness, cerebral palsy and mental retardation. In utero infection presents with no clinical symptoms 90% of the time. However, 5% do exhibit atypical illness and the other 5% with typical CMV damage including hepatitis, gestational prematurity, microcephaly, anemia, intracranial calcifications and intrauterine growth retardation.
CMV is thought to induce these malformations through mechanisms similar to the rubella virus; i.e., cell lysis and immune response.
In utero infection with herpes has become an uncommon even in the past few years. Congenital herpes infection may be prevented by cesarean section in mothers with active lesions.
Insulin-dependent diabetes has been linked to multiple congenital malformations such as cardiac and skeletal (appendicular and axial) malformations, central nervous system alterations (holoprosencephaly) and caudal dysgenesis (agenesis of sacral vertebrae and hind limb hypoplasia). Twenty-five percent of all cases of hydramnios (excess amniotic fluid) are due to maternal diabetes. The risk of malformation is 3-4 times that of a normal pregnancy. Disturbed carbohydrate metabolism has been associated with an increased risk of stillbirth, neonatal deaths and abnormally large infants.
Diabetes controlled by insulin severely reduces the risk of congenital malformation. Therapy should begin well before conception to ensure a normal fetus. The mechanism of these malformations has not been fully elucidated, but it has been shown that it is the alteration in glucose levels and not the insulin which is teratogenic. A neurulating or gastrulating mammalian embryo is critically dependant upon maternal glucose levels. Even brief periods of decreased glucose concentrations are teratogenic.
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