Perinatal infection

# Overview
perinatal infections represent the most important  causes of permanent disability among children worldwide. Referred to it  by the acronym TORCH, denoting Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus,etc, it can result in  congenital infections from only a modest number of human pathogens which cross the placenta and infect the fetus. Although congenital rubella syndrome has been eliminated in the Americas by immunization, several pathogens discussed in this chapter cannot currently
be prevented by vaccines or effectively treated with the available antimicrobial drugs. Due to the immaturity of the immune system, newborn infants are at risk for postnatally acquired infections with certain viruses and several bacteria. This chapter summarizes the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of selected pathogens that can damage the developing nervous system. As emphasized by the persisting challenges of preventing congenital cytomegalovirus infection and the emergence of severe brain damage associated with congenital Zika syndrome, these pathogens remain important causes of cerebral palsy, epilepsy, and intellectual disability.

# Historical Perspective

## Discovery
- over 100 years, The concept that there is certain human pathogens are able to damage the developing nervous system in utero or perinatally. Although  female can get numerous infectious agents during their pregnancies, relatively few pathogens cross the placenta and cause intrauterine fetal infections.
- In the 1970s, There is investigators at Emory University and the Centers for Disease Control and Prevention (CDC) coined the term TORCH, an acronym underscoring Toxoplasma gondii, rubella virus, cytomegalovirus, and herpesvirusesas important, potential causes of congenital infection.
- The TORCH concept highlighted that these agents can produce the same clinical manifestations in infected infants.
- Although congenital rubella virus syndrome has disappeared in countries with compulsory immunization against this virus , the TORCH agents, as well as more recently recognized pathogens, such as lymphocytic choriomeningitis virus and Zika virus, remain major causes of long-term neurodevelopmental disabilities among children throughout the world.

# Classification
Perinatal infection is vertically transmitted infection ,which starts at gestational ages between 22 and 28 weeks (with regional variations in the definition) and ending seven completed days after birth

# Pathophysiology
- In the scale of optimal virulence, vertical transmission tends to progress benign symbiosis, so is a critical idea for evolutionary medicine. Because the ability of reproducibility of  pathogen  in the host is  the leading cause of pathogen  to pass from mother to child, Its transmissibility tends to be inversely related to their virulence.
- Although HIV is transmitted through perinatal transmission, it is vertical transmission is not the primary mode of transmission. in addition to the new medicine decreased the frequency of vertical transmission of HIV. The incidence of perinatal HIV cases in the United States has decreased as a result of the implementation of recommendations on HIV counselling and voluntary testing practices and the use of zidovudine therapy to reduce perinatal HIV transmission.
- In dual inheritance theory, vertical transmission refers to the passing of cultural traits from parents to children.

# Causes
the following  organism responsible for perinatal infection are transmitted either by one of the following across the placenta (transplacental) and across the female reproductive tract during (childbirth).

## Transplacental
The embryo and fetus have little or no immunity and depend on the immune function of their mother. Several pathogens can cross the placenta and cause perinatal infection. Often, microorganisms that produce minor illness in the mother are very dangerous for the developing embryo or fetus.

## During childbirth
Babies can also become infected by their mothers during  child birth. Some infectious agents may be transmitted to the embryo or fetus in the uterus, while passing through the birth canal, or even shortly after birth.

# Types of infections
Bacteria, viruses, and other organisms are able to be passed from mother to child. Several vertically transmitted infections are included in the TORCH complex:
- T  toxoplasmosis from Toxoplasma gondii
- O  other infections (see below)
- R  rubella
- C  cytomegalovirus
- H  herpes simplex virus-2 or neonatal herpes simplex
Other infections include:
- Parvovirus B19
- Coxsackievirus
- Chickenpox (caused by varicella zoster virus)
- Chlamydia infection
- HIV
- Human T-lymphotropic virus
- Syphilis
- Zika fever, caused by Zika virus, can cause microcephaly and other brain defects in the child.
- Hepatitis B
The TORCH complex was originally considered to consist of the four conditions mentioned above, with the "TO" referring to Toxoplasma. The four-term form is still used in many modern references and the capitalization "TORCH" is sometimes used in these contexts.
- A further expansion of this acronym, CHEAPTORCHES, was proposed by Ford-Jones and Kellner in 1995:
- C  chickenpox and shingles
- H  hepatitis, C , (D), E
- E  enteroviruses
- A  AIDS (HIV infection)
- P  parvovirus B19 (produces hydrops fetalis secondary to aplastic anemia)
- T  toxoplasmosis
- O  other (group B streptococci, Listeria, Candida, and Lyme disease)
- R  rubella
- C  cytomegalovirus
- H  herpes simplex
- E  everything else sexually transmitted (gonorrhea, Chlamydia infection, Ureaplasma urealyticum, and human papillomavirus)
- S  Syphilis

# Differentiating types of perinatal infection

# Epidemiology and Demographics

## Age
- Patients of all age groups may develop perinatal infection.

## Gender
- perinatal infection affects  boy and girls children  equally.

## Race
- There is no racial predilection for perinatal infection.

# Risk Factors
- Common risk factors in the development of Perinatal infection. are
Infant outcomes
In addition, we evaluated combined grade 3 and grade 4 intraventricular hemorrhage and combined stages 3 through 5 ROP to align with common categorization of these more clinically important outcomes.

# Natural History, Complications and Prognosis
Early clinical features include
-: not seen; +/: rare; +: occasional; ++: common; +++: very common. 

# Diagnosis

## Diagnostic Criteria
- The diagnosis of  is made when
Chlamydia can be diagnosed by taking a cotton swab sample of the cervix and vagina during the third trimester of the pregnancy. Chlamydial cell cultures take three to seven days to grow. DNA probes are available for more rapid diagnosis.
- Past or recent infection with cytomegalovirus (CMV) can be identified by documentation of seroconversion of a previously seronegative patient (the development of IgG antibodies to CMV in a patient who was previously negative for these antibodies)  and CMV can be grown from body fluids. 
- Genital herpes is suspected with the outbreak of a particular kind of genital sore. The sore can be cultured and tested to confirm that HSV-2 is present.
- Hepatitis B can be identified through a blood test for the hepatitis B surface antigen (HBsAg) in pregnant women. The test is part of prenatal health programs.
- Human immunodeficiency virus (HIV) can be detected using a blood test and is part of most prenatal screening programs.
- Human papillomavirus (HPV) causes the growth of warts in the genital area. The wart tissue can be removed with a scalpel and tested to determine what type of HPV virus caused the infection.
- Pregnant women are usually tested for antibodies to rubella, which would indicate that they have been previously exposed to the virus and, therefore, would not develop infection during pregnancy if exposed.
- Group beta streptococcus (GBS) can be detected by a vaginal or rectal swab culture and sometimes from a urine culture. Blood tests can be used to confirm GBS infection in infants who exhibit symptoms.
- Pregnant women are usually tested for syphilis as part of the prenatal screening, generally with a blood test.
- ZIKA virus Methods for testing include both serologic and molecular tests. Laboratory tests in include ZIKV IgM, ZIKV NAT, and plaque reduction neutralization testing.

## History and Symptoms
If a developing fetus is infected by a TORCH agent, the outcome of the pregnancy may be miscarriage, stillbirth, delayed fetal growth and maturation (intrauterine growth retardation), or early delivery.
In addition, newborns infected by any one of the TORCH agents may develop a spectrum of similar symptoms and findings. These may include
- listlessness (lethargy),
- fever,
- difficulties feeding,
- hepatosplenomegaly,
- anemia.
In addition, affected infants may develop
- petechia or purpura;
- jaundice;
- chorioretinitis; and/or other symptoms and findings.
Each infectious agent may also cause additional abnormalities that may vary in degree and severity, depending upon the stage of fetal development at time of infection and/or other factors.  
Following is a more specific description of the TORCH agents.
 Classic triad of toxoplasmosis Chorioretinitis (a form of posterior uveitis), Diffuse intracranial calcifications, Hydrocephalus
  Rubella is a viral infection characterized by fever, upper respiratory infection, swelling of the lymph nodes, skin rash, and joint pain. Severely affected newborns and infants may have visual and/or hearing impairment, heart defects, calcium deposits in the brain, and/or other abnormalities.  
  Cytomegalovirus (CMV) Infection is a viral infection associated finding: growth retardation, microcephaly, hepatosplenomegaly, hepatitis, hemolytic anemia, calcium deposits in the brain.
  Herpes simplex virus   may lead to neonatal herpes. the disorder is transmitted to an infant from an infected mother with active genital lesions at the time of delivery. In the event that a mother has a severe primary genital outbreak, it is possible that a mother may transmit the infection to the fetus. Severely affected newborns may develop cutaneous vesicles in the mouth area, conjunctivitis, abnormally diminished muscle tone,  hepatitis, difficulties breathing.
  Parvovirus B19 Infection can cause miscarriage, fetal anemia, hydrops fetalis, myocarditis, and/or intrauterine fetal death.
 Syphilis Early congenital syphilis: Hepatomegaly and jaundice, Rhinorrhea with white or bloody nasal discharge , Maculopapular rash on palms and soles , Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis) Generalized lymphadenopathy (nontender).
  listeriosis Increased risk of premature birth and spontaneous abortion ,Early-onset syndrome: granulomatosis infantiseptica ,Severe systemic infection ,Most common findings: respiratory distress and skin lesions, Signs of meningitis may already develop. 
  enterovirus Wide spectrum of clinical presentations, from non-specific febrile illness to fatal  multisystem disease, Fever, irritability, poor feeding, lethargy, Maculopapular rash in 50%  ,Respiratory symptoms in 50% ,Gastrointestinal symptoms in 20% , Hepatitis in 50% ,may have myocarditis, meningoencephalitis

## Physical Examination

## Laboratory Findings
- rubella may be diagnosed by detection of specific IgM, but virus detection is the technique of choice.
- VZV may be diagnosed by serological techniques in up to 71% of cases. Detection of virus in vesicle scrapings or swabs from the oropharynx is the technique of choice for neonatal HSV.
- enterovirus infections are best diagnosed by detection of viral RNA.
- HIV-1 may be diagnosed within 3 months of birth by testing serial blood samples with a combination of techniques. Maternal infection with HBV, HCV, HIV and HTLV1/11 may be diagnosed by serological techniques and genital PVs by detection of viral DNA. Chorionic villus samples, amniotic fluid and fetal blood may be obtained for prenatal diagnosis of infection.
- detection of virus in amniotic fluid is the technique of choice for prenatal diagnosis of CMV, insufficient data is currently available to determine whether it may be used for intrauterine rubella.
- The most reliable technique for diagnosis of fetal B19 infection is detection of viral DNA .
the use of TORCH screening should be discouraged.

## Electrocardiogram
There are no ECG findings associated with .

## X-ray
There are no x-ray findings associated with perinatal infection.

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound  findings associated with  perinatal infection. CT scan may be helpful in the diagnosis of Toxoplasmosis include dilated ventricles with multiple subependymal and parenchymal calcifications .
MRI may be helpful in the diagnosis of ]]. Findings on MRI suggestive of/diagnosis include  ring enhanced lesion
- Caption1
Imaging features of selected congenital infections 
CMV=cytomegalovirus; LCM virus =lymphocytic choriomeningitis virus. (-) absent; (+) uncommon or rare; (++) common; (+++) very
common.
There are no other diagnostic studies associated with perinatal infection

# Treatment

## Prevention
Minimizing the risk of transmitting a maternal infection to a fetus is often a major concern for parents. The first step is identifying possible maternal infections. Proper prenatal care in many cases allows for early diagnosis and thus early treatment of certain infections, thus improving the newborn's prognosis 
A woman's nutritional status may contribute to her ability to fight off infections, particularly in cases of malnutrition . A well-balanced diet rich in nutrients such as folic acid , calcium, iron, zinc, vitamin D, and the B vitamins is recommended for pregnant women. Mothers are recommended to eat approximately 300 additional calories day (above and beyond a normal non pregnancy diet) to support the fetus's growth and development