Embryology, Teratology TORCH


Article Author:
Briana Belanger


Article Editor:
Forshing Lui


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
8/16/2019 6:23:51 PM

Introduction

Teratology is the study of congenital abnormalities, their causes, and the treatment options available for those affected.[1] These abnormalities are principally the result of infections, physical agents, metabolic conditions or chemicals and can cause death as well as physical, behavioral, and intellectual deficits.[2] The most widely accepted infectious teratogens are known as TORCH infections. If a woman is infected prenatally, perinatally, peripartum, or even postnatally, these pathogens are known to cause congenital birth defects. 

TORCH infections classically include:

  • Toxoplasmosis
  • Other Infections (Varicella, syphilis and Parvovirus B19)
  • Rubella
  • Cytomegalovirus (CMV)
  • Herpes simplex virus (HSV)

TORCH infections have also been known to include Treponema pallidum, Hepatitis viruses, and human immunodeficiency virus (HIV).[3]

Development

In addition to passing horizontally (from person to person), TORCH infections can also transmit vertically (from mother to infant). When a pregnant woman becomes infected, the infection can spread to her unborn fetus. Generally, the earlier the exposure to the teratogen, the more deleterious its effects. Infection during the first trimester is likely to cause a more severe version of the congenital defects in the growing embryo. The later in pregnancy that an infection occurs, the more likely that the fetus will develop a neonatal infection rather than develop congenital abnormalities.[3]

Cellular

Transmission of viral or bacterial agents from mother to fetus is often transplacental, but the means by which these particles can cross the placenta and affect the fetus is not fully understood.[4][5]

Mechanism

Toxoplasmosis:

Toxoplasmosis results from infection with the parasite Toxoplasma gondii. This parasite goes through its reproductive stages in the intestines of the Felidae family and then gets expelled as an oocyst into the environment. Then, these oocysts cause toxoplasmosis through inhalation of fecal particles or by the ingestion of infected tissue. After infection of the mother, there is a transplacental transmission of the parasite to the fetus causing congenital toxoplasmosis. The likelihood of infection is the highest in the third trimester but the earlier in the pregnancy that the infection occurs, the more severe the manifestation of the congenital birth defects.[6][7]

Other:

Varicella-zoster virus (VZV) is an airborne DNA virus of the herpesvirus group that spreads by sneezing, coughing, or contact with active lesions.[8] It also passes from mother to fetus transplacentally.[9] There is an estimated 2% chance that an infant will develop congenital varicella syndrome if the mother contracts VZV during the first two trimesters.[10]

Syphilis is an infection of the spirochete Treponema pallidum and spreads by sexual exposure or vertical transmission. Vertical transmission most commonly occurs transplacentally but can also occur due to peripartum exposure to vaginal fluid. In women recently infected with syphilis, the probability of transmission is more than 80%.[11]

Parvovirus B19, a single-stranded DNA virus, is the only member of the Parvoviridae family that is pathogenic in humans. It passes through respiratory droplets, blood exposure, or vertically transmitted through the placenta.[12][13]

Rubella:

Rubella is a single-stranded, positive-sense RNA virus that gets transmitted from infected individuals through aerosols. It also passes from the infected mother to the fetus transplacentally.[14]

CMV:

CMV is a human-specific double-stranded DNA virus of the Herpesviridae family. Horizontal transmission is via the mucous membrane, blood transfusions or, organ transplants. It can pass from mother to fetus transplacentally but also from contact with cervical or vaginal secretions during the birthing process or by breastmilk postnatally. Though rarer, a woman with a latent CMV infection can infect her fetus if she becomes infected with an additional strain during pregnancy.[15]

HSV:

HSV-1 and HSV-2 are large, enveloped double-stranded DNA viruses. These viruses are passed from direct contact with mucous membranes, saliva or sores and can occur despite a lack of active infection. Once acquired, the virus often is asymptomatic or non-specific, which leads to the spread of the infection due to a lack of proper precautions. HSV-1 is more commonly found orally, while HSV-2 is more often a genital infection, but infection of either virus can occur anywhere on the body. This virus is primarily passed to the infant during delivery when the mother has an active infection with sores but has been known to occur during latent infections. While episodes of active HSV can be relatively rare after initial infection, pregnancy often triggers active infection in approximately 75% of HSV positive women. Infants born to mothers initially infected with HSV in the third trimester of pregnancy are at the highest risk for contracting neonatal HSV.[16][17]

Testing

Toxoplasmosis:

Diagnosing a patient with congenital toxoplasmosis requires proving the presence of either the parasite itself, through PCR, microscopy or inoculation, or by identifying the toxoplasma gondii specific IgG, IgM or IgA humoral response. Brain imaging (calcifications, hydrocephaly, and microcephaly) and retinal exams (chorioretinitis) can be used to determine the severity of symptoms but are not considered diagnostic.[3][18]

Other:

The mother’s history of chickenpox clinically confirms congenital varicella syndrome (CVS) during the pregnancy and the presence of congenital skin lesions following dermatomes in the infant. It is also diagnosable by detecting VZV DNA in either amniotic fluid or fetal blood.[19]

Congenital syphilis diagnosis is by a combination of serology and the presence of clinical symptoms. Often this diagnosis is presumptive, and an infant will need to be periodically checked by a physician if it is at risk for congenital syphilis.[20]

Congenital parvovirus B19 is most accurately diagnosed using a PCR assay to isolate parvovirus B19 DNA in the amniotic fluid or fetal blood. Clinicians can measure it with IgM antibody serology.[21]

Rubella:

To diagnose a patient with congenital rubella, the virus itself can be isolated, through PCR or culture, or the virus’ RNA can be isolated through reverse transcriptase PCR of bodily fluids. The presence of rubella specific IgM and IgG is also enough to base a diagnosis of congenital rubella.[3]

CMV:

Despite the high disease burden, there are still no screening programs for mothers or infants to detect CMV infections. In infants, clinical symptoms can go absent or can be ambiguous enough not to suspect congenital CMV. In the past, testing for congenital cytomegalovirus involved using urine or saliva samples to isolate the virus in tissue cultures.[22] More recently, real-time PCR, which gets repeated if positive, is being used to detect the virus, which is less resource-intensive and could potentially support more widespread screening in the future.[23] In pregnant women, CMV diagnosis can also be through CMV specific IgM and IgG serology.[24]

HSV:

Congenital HSV is detected by either HSV isolation on culture or by PCR. Today, PCR is becoming a more common test due to its more accurate and precise ability to diagnose an HSV infection. Screening for HSV antibodies is problematic as it is not type-specific, and oral HSV-1 infections are prevalent and do not pose the same risk as a genital HSV-2 infection.[25] 

TORCH IgG or IgM Panel Testing:

There are lab panels collectively performed to look for specific IgM or rising IgG titers in fetal, cord, or infant blood. The panel will include antibody testing for Toxoplasmosis, Rubella, CMV, HSV 1/2, and VZV. Positive tests will indicate congenital infection by one of these agents. These are more straightforward and easier tests to be performed collectively for any neonate suspected clinically to be suffering from the above named congenital infections.

Clinical Significance

Toxoplasmosis:

A perinatal, or more rarely prenatal, initial infection of Toxoplasma gondii classically causes a baby to be born with retinal lesions, hydrocephalus, and intracranial calcifications but is also associated with anemia, jaundice, hepatosplenomegaly, and thrombocytopenia. Approximately 75% of those infected in utero will be asymptomatic at birth, but as they grow, they will be at significant risk for developing motor dysfunction, cerebellar dysfunction, microcephaly, seizures, chorioretinitis, intellectual disabilities, and sensorineural hearing loss.[26] Toxoplasmosis in healthy adults is typically asymptomatic.[3] The prevalence of congenital toxoplasmosis is approximately 0.1 to 0.01 per 1000 live births and is attributable to pregnant women eating undercooked meat and cleaning cat litter boxes.[3]

Other:

Despite there being 60 million new cases of varicella infection each year, CVS is rather rare, only 130 cases reported since 1947, but mortality rates are 30% in the first few months. CVS often causes skin lesions, limb hypoplasia, neurological abnormalities, and developmental delay. There is no evidence that infants born asymptomatic will develop symptoms in the future.[27][28]

Syphilis infects 5.6 million people per year.[11] Pregnancies where the woman contracts syphilis and is not treated result in stillbirth 25% of the time, neonatal death 14% of the time and in 41% of cases the infant is born with congenital syphilis. Congenital syphilis can result in neurodevelopmental deficits, musculoskeletal deformities as well as renal and gastrointestinal issues. The classical Hutchinson triad described in infants with congenital syphilis consists of Hutchinson teeth (small, peg-shaped, notched upper incisors), interstitial keratitis and sensorineural hearing loss. There is only a 20% chance that an untreated affected mother will have a healthy infant. The longer the fetus is exposed to T. pallidum in utero the bleaker the outcome. Pregnant women can be treated with benzathine penicillin G to diminish the bacterial load and decrease the likelihood of complications during pregnancy.[20]

Parvovirus B19 only affects 1 to 5% of pregnant women, but the consequences can be devastating. This infection can lead to spontaneous abortion, severe neurodevelopmental deficits, and hydrops fetalis but 67 to 76% of infants are born to mothers infected with parvovirus B19 are unaffected.[21][12]

Rubella:

Infants perinatally infected with rubella are often asymptomatic but may later develop hearing loss, blindness, heart defects, encephalitis, endocrinopathies as well as behavioral and intellectual deficits. Children suspected of having congenital rubella must be surveilled carefully for the onset of new symptoms. The prevalence of congenital rubella is as high as approximately 175 per 100000 live births in the developing Americas.[29][30][31] In general, the earlier the fetus is infected with rubella during pregnancy, the more severe the congenital deficits are. Up to 85% of babies born to mothers infected with rubella during the first trimester may develop the congenital rubella syndrome which consists of sensorineural deafness, cataracts, congenital heart problems, central nervous system deficits, impaired mental development, bone defects, and hepatosplenomegaly. 

CMV:

Though commonly asymptomatic in healthy adults, CMV affects an estimated 60% of people in the United States (age-adjusted).[32] Additionally, CMV is the number one cause of infection-induced birth defects. Congenital CMV affects one in every 150 live births globally.[33] CMV is also the leading cause of nongenetic congenital hearing loss. Approximately 7 to 10% of infants with congenital CMV develop clinical manifestations. These include petechiae, jaundice, hepatosplenomegaly, chorioretinitis as well as neurological deficits, which consists of physical and mental retardation, deafness, and even death in about 10% of patients. Many of these infants are born asymptomatic and lack proper screening for congenital CMV. They are likely to develop these issues later in life. It is common practice to treat symptomatic CMV positive infants with six months of valganciclovir. Asymptomatic infants customarily receive no treatment.[34][23][15][22] 

HSV:

Approximately 50 to 70% of people in developed countries and nearly 100% of those in developing countries are seropositive for oral herpes simplex virus (HSV-1). Genital herpes simplex virus (HSV-2) is present in approximately 10 to 40% of the population and about 22% of pregnant women.[16][25] These viruses affect a huge percentage of the population and are incurable and require lifetime management. Neonatal herpes is uncommon, but symptoms are severe and can be deadly. Symptoms include viral sepsis, organ failure (lung, liver), disseminated intravascular coagulation, encephalitis, vesicular rash, seizures, bulging fontanelle, and death. Acyclovir, an anti-viral treatment, is available for affected infants but must be administered promptly to afford the most protection to the infant. If an HSV infection is suspected, a cesarean delivery is the recommended approach as 85% of neonatal HSV infection is peripartum.[16]


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A pregnant woman who is a vegetarian with no history of travel or insect bites comes in with complaints of severe flu-like symptoms for the past four days. A complete blood count (CBC) is done and results are RBC of 4 million/mm3, leukocyte count 7,000/mm3, segmented neutrophils 55%, bands 4%, eosinophils 5%, basophils 0%, lymphocytes 32%, and monocyte 4%. Other blood tests reveal a hemoglobin of 3 mg/dL, hematocrit 40%, MCV 85 um3, and platelets 300,000/mm3. What would be the main concern for this case?



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A neonate was born full-term by vaginal delivery to a 28-year-old woman. The woman has multiple sexual partners and did not practice any protection during sex. She was not sure who the baby's father is. What is the most common eye condition shown in the neonate that will lead to the diagnosis of an intrauterine infection?



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A 30-year-old woman gave birth to a 7 lbs infant boy by spontaneous vaginal delivery. The neonate is noted to have a purpuric rash, abnormal eye findings on fundoscopy and hepatosplenomegaly. An intrauterine TORCH infection is suspected. What is the best diagnostic test to confirm these intrauterine infections?



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Embryology, Teratology TORCH - References

References

Ujházy E,Mach M,Navarová J,Brucknerová I,Dubovický M, Teratology - past, present and future. Interdisciplinary toxicology. 2012 Dec;     [PubMed]
Calado AM,Dos Anjos Pires M, An Overview of Teratology. Methods in molecular biology (Clifton, N.J.). 2018;     [PubMed]
Neu N,Duchon J,Zachariah P, TORCH infections. Clinics in perinatology. 2015 Mar;     [PubMed]
Montoya JG,Liesenfeld O, Toxoplasmosis. Lancet (London, England). 2004 Jun 12;     [PubMed]
Halonen SK,Weiss LM, Toxoplasmosis. Handbook of clinical neurology. 2013;     [PubMed]
Ayoade F,Kumar S, Varicella Zoster (Chickenpox) 2019 Jan;     [PubMed]
Marculescu R,Richter L,Rappersberger K, [Infections with herpes simplex and varicella-zoster viruses during pregnancy]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2006 Mar;     [PubMed]
Sauerbrei A,Wutzler P, The congenital varicella syndrome. Journal of perinatology : official journal of the California Perinatal Association. 2000 Dec;     [PubMed]
Peeling RW,Mabey D,Kamb ML,Chen XS,Radolf JD,Benzaken AS, Syphilis. Nature reviews. Disease primers. 2017 Oct 12;     [PubMed]
Heegaard ED,Brown KE, Human parvovirus B19. Clinical microbiology reviews. 2002 Jul;     [PubMed]
Pattison JR,Patou G, Parvoviruses 1996;     [PubMed]
Parkman PD, Togaviruses: Rubella Virus 1996;     [PubMed]
Schottstedt V,Blümel J,Burger R,Drosten C,Gröner A,Gürtler L,Heiden M,Hildebrandt M,Jansen B,Montag-Lessing T,Offergeld R,Pauli G,Seitz R,Schlenkrich U,Strobel J,Willkommen H,von König CH, Human Cytomegalovirus (HCMV) - Revised. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2010;     [PubMed]
Pinninti SG,Kimberlin DW, Preventing herpes simplex virus in the newborn. Clinics in perinatology. 2014 Dec;     [PubMed]
Stankiewicz Karita HC,Moss NJ,Laschansky E,Drolette L,Magaret AS,Selke S,Gardella C,Wald A, Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy. Open forum infectious diseases. 2017 Fall;     [PubMed]
Pomares C,Montoya JG, Laboratory Diagnosis of Congenital Toxoplasmosis. Journal of clinical microbiology. 2016 Oct;     [PubMed]
Hartung J,Enders G,Chaoui R,Arents A,Tennstedt C,Bollmann R, Prenatal diagnosis of congenital varicella syndrome and detection of varicella-zoster virus in the fetus: a case report. Prenatal diagnosis. 1999 Feb;     [PubMed]
Arnold SR,Ford-Jones EL, Congenital syphilis: A guide to diagnosis and management. Paediatrics     [PubMed]
Giorgio E,De Oronzo MA,Iozza I,Di Natale A,Cianci S,Garofalo G,Giacobbe AM,Politi S, Parvovirus B19 during pregnancy: a review. Journal of prenatal medicine. 2010 Oct;     [PubMed]
Marsico C,Kimberlin DW, Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Italian journal of pediatrics. 2017 Apr 17;     [PubMed]
Dietrich ML,Schieffelin JS, Congenital Cytomegalovirus Infection. The Ochsner journal. 2019 Summer;     [PubMed]
Munro SC,Hall B,Whybin LR,Leader L,Robertson P,Maine GT,Rawlinson WD, Diagnosis of and screening for cytomegalovirus infection in pregnant women. Journal of clinical microbiology. 2005 Sep;     [PubMed]
LeGoff J,Péré H,Bélec L, Diagnosis of genital herpes simplex virus infection in the clinical laboratory. Virology journal. 2014 May 12;     [PubMed]
McAuley JB, Congenital Toxoplasmosis. Journal of the Pediatric Infectious Diseases Society. 2014 Sep;     [PubMed]
Lamont RF,Sobel JD,Carrington D,Mazaki-Tovi S,Kusanovic JP,Vaisbuch E,Romero R, Varicella-zoster virus (chickenpox) infection in pregnancy. BJOG : an international journal of obstetrics and gynaecology. 2011 Sep;     [PubMed]
Wondimeneh Y,Tiruneh M,Ferede G,Denekew K,Admassu F,Tessema B, Hospital based surveillance of congenital rubella syndrome cases in the pre-vaccine era in Amhara Regional State, Ethiopia: A base line information for the country. PloS one. 2018;     [PubMed]
Toizumi M,Vo HM,Dang DA,Moriuchi H,Yoshida LM, Clinical manifestations of congenital rubella syndrome: A review of our experience in Vietnam. Vaccine. 2019 Jan 3;     [PubMed]
Cutts FT,Vynnycky E, Modelling the incidence of congenital rubella syndrome in developing countries. International journal of epidemiology. 1999 Dec;     [PubMed]
Cheeran MC,Lokensgard JR,Schleiss MR, Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clinical microbiology reviews. 2009 Jan;     [PubMed]
Permar SR,Schleiss MR,Plotkin SA, Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections. Journal of virology. 2018 Apr 1;     [PubMed]
Whitley RJ, Congenital Cytomegalovirus and Neonatal Herpes Simplex Virus Infections: To Treat or Not to Treat? The Pediatric infectious disease journal. 2019 Jun;     [PubMed]
Robbins JR,Bakardjiev AI, Pathogens and the placental fortress. Current opinion in microbiology. 2012 Feb;     [PubMed]
Pereira L, Congenital Viral Infection: Traversing the Uterine-Placental Interface. Annual review of virology. 2018 Sep 29;     [PubMed]
Papaloukas O,Giannouli G,Papaevangelou V, Successes and challenges in varicella vaccine. Therapeutic advances in vaccines. 2014 Mar;     [PubMed]

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