Transcript for Perinatal infections
Perinatal infections are a significant cause of impaired growth, developmental anomalies, and mortality. They can be divided into two categories.
The first category is in-utero infections acquired transplacentally or through ruptured membranes, which lead to congenital defects. They are mostly represented by TORCH infections, an acronym that includes infections caused by Toxoplasma, Other agents - usually syphilis; Rubella; Cytomegalovirus, and Herpes simplex virus.
The second category belongs to intrapartum infections, which are acquired as the newborn passes through the birth canal, mostly caused by group B streptococcus, Hepatitis B virus, and HIV.
Let’s begin with TORCH infections. In some cases, intrauterine infection may be suspected on the basis of laboratory results obtained during pregnancy, like positive syphilis serology with increasing titers, and on ultrasonography findings.
After birth, although most infections are asymptomatic, common early signs include fever, microcephaly, cataract, hearing loss, congenital heart disease, hepatosplenomegaly, thrombocytopenia, and jaundice. Late signs include vision loss, intellectual disability, deafness, and seizures.
First, congenital toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. Prenatal diagnosis is based on ultrasonography signs of congenital infection, like ventriculomegaly, intracranial calcifications, and fetal growth restriction. It is then confirmed by polymerase chain reaction or PCR testing of the amniotic fluid.
If PCR doesn’t confirm the presence of Toxoplasma DNA, those suspected of congenital toxoplasmosis will still need a complete diagnosis evaluation after birth. Postnatal diagnosis evaluation begins with a complete clinical examination.
The most common early and late symptoms are cataract, microcephaly, hepatomegaly, jaundice, and purpura. Evaluation continues with serologic tests performed as soon as possible after birth. These consist of Toxoplasma immunoglobulin G plus Toxoplasma-specific immunoglobulin M and immunoglobulin A assays using peripheral blood. Also, neonatal Toxoplasma IgG antibodies should be tested in parallel with maternal Toxoplasma IgG antibodies to aid interpretation.
Ok so congenital infection is confirmed by positive IgG alongside positive IgM and IgA.
If the individual has clinical findings suggestive of congenital infection, positive IgG but negative IgM and IgA, they are presumed to be infected. This is because there might be a delay in IgM and IgA production. Repeat testing can help exclude congenital toxoplasmosis if, in the absence of treatment, it shows a decline in IgG titer and negative Toxoplasma-specific IgM or IgA after one year of life.
Next, if data is inconclusive but there are clinical signs of congenital toxoplasmosis; a positive maternal history of infection; or if lab results came back positive, lumbar puncture is needed to obtain cerebrospinal fluid for Toxoplasma PCR, protein, glucose, and cell count.
If PCR is positive, it confirms the diagnosis. Laboratory analysis of the cerebrospinal fluid might show elevated protein above 1 gram per decilitre or mononuclear pleocytosis.
Ok, after that, brain CT is performed to look for focal brain lesions or hydrocephalus, which is characterized by an accumulation of cerebrospinal fluid within the brain.
Other findings may include intracranial calcifications and cortical atrophy.
An ophthalmological examination is also needed to look for chorioretinitis which is the inflammation of the choroid and retina of the eye as that might be the only sign of infection in newborns. I
f chorioretinitis, hydrocephalus, and intracranial calcifications were detected, this is highly suggestive of congenital toxoplasmosis.
And finally, all newborns with suspected congenital toxoplasmosis should undergo hearing evaluation since it can lead to hearing loss.
Prenatal management consists of spiramycin therapy in those under 18 weeks of gestation to prevent maternal transmission. Pyrimethamine and sulfonamides can be used later in gestation to treat the infected fetus.
Newborn management consists of a regime of three antiparasitic drugs. First, pyrimethamine is given in doses of 2 milligrams per kilogram orally once a day for 2 days, which is then reduced to 1 milligram per kilogram for six months. After six months, therapy is continued for another six months with a dose of 1 milligram per kilogram three times a week. Leucovorin is usually administered in doses of 10 milligrams 3 times a week for one year and a week, and sulfadiazine is given in doses 50 milligrams per kilogram twice a day just for one year. Glucocorticoids like prednisone 0.5 milligrams twice per day are added if cerebrospinal fluid protein is above 1 gram per decilitre or when chorioretinitis causes vision problems.
Next, congenital syphilis is caused by the spirochete Treponema pallidum.
Prenatal diagnosis is based on ultrasonography findings and on the same tests as in postnatal diagnosis but using umbilical cord samples. After birth, evaluation begins with a complete physical examination.
Clinical findings can be divided arbitrarily into early signs which appear under or around two years of age; and late which appear after two years of age.
More specific early signs might include a large, thick, and pale placenta; generalized, nontender lymphadenopathy; bone deformities; and rhinitis. A maculopapular rash consisting of small, red or pink spots also might appear one to two weeks after rhinitis. The rash progresses over one to three weeks, and it is followed by desquamation and crusting. If present at birth, it may be widely disseminated and bullous. The umbilical cord might edematous and resemble a "barber's pole" with spiral stripes of red and light blue alternating with white discoloration. Long-bone abnormalities associated with pathologic fractures or pain giving the appearance of paralysis might be present as well.
Regarding late signs, they can develop anywhere, including the face - represented by frontal bossing where the forehead is really prominent, saddle nose, or short maxilla; the eyes, where syphilis manifests as interstitial keratitis, secondary glaucoma, and corneal scarring; the ears, where it leads to hearing loss; oropharynx – presenting as the Hutchinson triad, which is virtually pathognomonic for congenital syphilis.
The triad consists of Hutchinson teeth which are small, notched, widely spaced permanent teeth; mulberry molars, described as molars with small cusps and enamel nodules; and of perforation of the hard palate.
Next, diagnosis can be confirmed by detecting spirochetes on darkfield microscopy or by PCR using samples from any mucosal lesion newborn or the placenta might present. If positive, diagnosis can be made. Now, if negative, serologic tests are needed.
First, nontreponemal tests like Rapid Plasma Reagin or RPR, which are based on the reactivity of the infected serum to a cardiolipin-cholesterol-lecithin antigen, can be ordered. If any nontreponemal serum test shows an antibody titer 4 times higher than the maternal titer value, alongside any typical symptom of congenital syphilis, infection is highly probable. If the titers are normal or lower but the individuals has typical clinical manifestations, syphilis is considered unlikely. In neonates with no signs of illness and low or negative serologic titers, syphilis is considered possible.
Second, treponemal tests like fluorescent treponemal antibody absorption or FT-ABS, which detect antibodies against specific treponemal antigens, are required to confirm any positive nontreponemal test result.
Next, those with clinical signs of congenital syphilis or born of infected mothers who received inadequate or no treatment should undergo subsequent testing, including long bone radiographic examination and lumbar puncture for cell count, protein, and non-treponemal tests.
Treatment under 1 month of age consist of a single dose of Penicillin G benzathine, 50,000 units per kilogram, intramuscularly. Those over 1 month of age require 50,000 units per kilogram of Penicillin G benzathine intravenously, every four to six hours for 10 days.
Third is congenital rubella infection which leads to congenital rubella syndrome in the newborn.
The prenatal diagnosis is based on specific findings on ultrasonography and positive rubella-specific IgM testing. After birth, evaluation begins with a clinical exam.
Common early signs include meningoencephalitis, large anterior fontanelle, cloudy cornea, cataract, glaucoma, and retinopathy.
Congenital rubella syndrome can be "confirmed," "infection only," or "probable," depending upon clinical findings and laboratory findings.
Evaluation begins with serologic tests. A high level of rubella-specific IgM antibody in those under six months of age or IgG in those between 6 and 12 months of age which persists for a longer time than expected from passive transfer of maternal antibody confirms diagnosis.
Next, viral detection using viral isolation from cultures based on nasopharyngeal secretions or PCR can be used instead of or together with serologic tests to confirm the diagnosis.
Other tests include a complete blood count with differential, lumbar puncture and cerebrospinal fluid analysis, and x-ray examination for bone anomalies.
Thorough ophthalmologic and cardiac evaluations are also useful in detecting associated congenital defects.
Those with symptoms consistent with CRS and negative serologic testing or viral detection, CRS is probable.
Treatment is mostly symptomatic. This means prevention is vital. Those who are planning on becoming pregnant should be vaccinated at least 28 days beforehand because the vaccine is a live virus.
Ok so congenital cytomegalovirus infection is diagnosed prenatally by viral culture, cytomegalovirus DNA detection on PCR or by cytomegalovirus-specific IgM antibody measurement in all of those who are symptomatic on ultrasonography.
Findings on ultrasound consist mostly of periventricular calcifications, ventriculomegaly, microcephaly, fetal growth restriction, and ascites or pleural effusion.
After birth, clinical examination usually reveals petechiae, jaundice, hearing loss, chorioretinitis, and seizures.
Cataracts and other severe eye problems are not found typical in congenital cytomegalovirus infection; if these are present, they strongly suggest another cause.
Next, laboratory diagnosis begins with PCR or viral isolation from cultures using urine samples collected within the first three weeks of life. If these come back positive, diagnosis can be confirmed. If inconclusive, repeat viral culture or PCR testing is required. If positive and the infant is under three weeks of age, diagnosis can be made. Alternatively, if the results are positive in a symptomatic infant older than three weeks, this suggests but does not confirm congenital cytomegalovirus infection because of the possibility of postnatal infection. The only way to confirm it is retrospectively by PCR analysis of dried blood samples or the so-called Guthrie cards obtained for newborn screening. If PCR comes back negative, the infection was acquired after birth.
Other lab tests are ordered to assess the extent of the infection. These include a liver panel which might show elevated liver transaminases, a full blood count revealing thrombocytopenia and lumbar puncture with cerebrospinal fluid analysis which may reveal elevated protein.
Neuroimaging consists mostly of ultrasonography, unenhanced CT or MRI, which might detect Intracranial calcifications, lenticulostriate vasculopathy, and white matter disease.
Treatment of symptomatic individual includes intravenous ganciclovir, usually 6 milligrams per kilogram every 12 hours. After six weeks, they can switch to oral valganciclovir, 16 milligrams per kilogram every 12 hours, for a total of six months.
And finally, neonatal herpes simplex virus infection is mostly acquired during birth. Congenital infection is possible too.
Prenatal diagnosis is based on specific ultrasonography findings and positive viral cultures or PCR.