Infections of the Fetus and Newborn

( Congenital and Perinatal infections ) By A. Badr- El - Din, M.D. Professor of Pediatrics & Neonatology Alexandria University

Introduction
Vertically transmitted ( mother to child ) infections of the fetus and newborn can generally be divided Into two major categories :  Congenital infections : which are transmitted to the fetus in utero.  Perinatal infections : which are acquired intrapartum or in the postpartum period.

Congenital Infections
Important points to remember: The time to provide information to mothers about these infections is before pregnancy begins, because this is the best time for preventive measures. 6. The first trimester is usually the most dangerous time to acquire these infections.
5.

3. Infection in the mother can often be

accompanied by trivial or even no symptoms, and the condition may not be remembered or diagnosed. 4.Infection in the mother does not always mean that the baby will be affected.

5.Some infections can be avoided by the mother through simple measures, e.g. immunization (Rubella, VZV ) during childhood and before pregnancy.

Etiologic Agents:
Viruses: CMV,HSV,VZV,Rubella, Hepatitis B virus, Parvovirus B19,HIV. Bacteria: Treponema pallidum, Listeria monocytogenes, Campylobacter fetus. Fungi: Candida albicans. Parasites: Toxoplasma gondii,Plasmodium spp., Trypanosoma cruzi.

The most common organisms causing Congenital Infections Include:

CMV, HSV, Parvovirus B19, Rubella, Hepatitis B virus, VZV, Toxoplasma gondii, HIV, Treponema pallidum

The acronym TORCH is not used any more. When suspected, the diagnosis of each of the possible infectious agents should be considered separately.

Pathogenesis
Pregnant women are exposed to infections in the community.  They are also more likely to be exposed to infections associated with young children.  These infants are often sick and represent a significant risk factor in exposure to infectious diseases.

The vast majority of these infections will usually resolve spontaneously or with appropriate antimicrobial agents and will not affect the developing fetus. However, if the infecting organism invades the blood stream, infection of the fetus may occur.

The most common means of infection of the fetus is via the blood stream. Less common means of infections include: * Extension from adjacent tissues and/organs.
*Invasive diagnostic or therapeutic interventions. ( e.g. monitors, fetal blood sampling, intrauterine transfusions )

Results of infection of the Embryo and Fetus

Death and resorption of the embryo.

 Abortion and stillbirth of the fetus. 

Live birth of a premature or term baby who may or may not be normal.

 The newborn may be L.B.W.

May have congenital anomalies. May have congenital disease. May have developmental abnormalities. The abnormalities may be apparent at birth or may not be recognized for months or years .

Syndromes in neonates caused by congenital infections Microorganism Signs
Toxoplasma gondii Rubella virus Cytomegalovirus
Hydrocephalus, diffuse intracranial calcification, chorioretinitis Cardiac defects, sensorineural hearing loss, cataracts Microcephalus, periventricular calcification Limb abnormalities, cicatricial lesions Diffuse edema (in utero hydrops fetalis) Vesicular lesions, keratoconjunctivitis Bullous, macular, and eczematous skin lesions involving the palms and the soles; rhinorrhea, dactylitis osteochondritis and periostitis.

Varicella - zoster virus
Erythrovirus B19 (Parvovirus B19)

Herpes simplex virus Treponema pallidum

Clinical signs of neonatal infections acquired in utero or at delivery
Clinical Sign Rubella virus CMV HSV Toxoplasma

Hepatospleno megaly

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Jaundice
Adenopathy

Pneumonitis

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Clinical sign

Rubella

CMV

HSV

TOXOPLA SMA

Microceph aly Hydroceph alus
Intracranial calcifications Hearing deficits

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Clinical sign
Skin lesions purpura

Rubella + _ _ +

CMV + + _ +

HSV + ++ + +

Toxoplasmosis

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Vesicles
Maculopa pular rash

CNS:
Meningoencephalitis

Cytomegalovirus ( CMV ) The most common cause of in-utero infection.  Fetal infection is greatest ( 40% ) during primary maternal infection & rarely during recurrent infection.  Only 10% of infants born with congenital infections are symptomatic at birth.  Infection during 1st trimester usually causes severe affection.

Survivors of this stage and a minority of asymptomatic infants will develop late complications.

A less severe form in the form of IUGR, microcephaly with or without I.C. calcification may be seen at birth. If the infection is acquired during labour the symptoms may appear after an I.P. of 4-12 wk or pass unnoticed only to be discovered with hearing abnormalities later. Transfusion acquired CMV can occur.

congenital CMV infection : microcephaly

Congenital cytomegalovirus infection and microcephaly in a neonate. Semi lateral skull radiograph shows intracranial calcifications that conform to the shape of the ventricles.

Diagnosis :  Culture.  PCR.  CMV IgM & IgG.  CT scan, abnormal CT predicts high probability of CNS sequalae. Treatment: Gancyclovir – valgancyclovir

Prevention :
Attenuated virus vaccine.  Hyper immune CMV immunoglobulin.

Breast milk :

Herpes – simplex virus ( HSV )
Two types of HSV: 1. HSV-1 ( Recurrent oro-labial disease ). 2. HSV-2 ( Recurrent genital disease ). Most mothers of infants with neonatal HSV DO NOT have a history of HSV.

IN-UTERO INFECTION of the fetus with HSV is RARE. The most severe IUI has a triad of:

1. Skin vesicles or scarring. 2. Eye disease : chorioretinitis, keratoconjunctivitis. 3. Microcephaly or hydrancephaly.

INTRA-PARTUM INFECTION : Responsible for 95% of cases : Always

symptomatic and frequently fatal particularly with primary maternal infection.

The risk of intra-partum transmission increases with ruptured membranes more than 4 hours.

Intra-partum and post-natal infection
may present with: 1. Disease localized to skin, eye, or mouth. 2. Encephalitis with or without skin ,eye or mouth involvement. 3. Disseminated infection of multiple organs.

Congenital HSV infection

Congenital HSV infection

DIAGNOSIS:

Specific IgM, DFA, CSF

MANAGEMENT:
1. Pregnant mothers: C/S in 1ry infection and when membranes are ruptured more than 4h. 2. Newborns at risk: Acyclovir for symptomatic NB, may be to asymptomatic as well pending laboratory evidence.

VARICELLA –ZOSTER VIRUS A. CONGENITAL VARICELL SYNDROME: Occurs if infection is acquired between 7-20 weeks gestation and characterized by: 1. Ocular defects. 2. CNS abnormalities. 3. IUGR. 4. Early death. These babies are unlikely to have an active viral disease and antiviral therapy is NOT indicated.

Congenital varicella infection

B. SEVERE DISEASE:
When varicella occurs in the mother in the 5 days before or in the 2 days after delivery.
  

Symptoms in the newborn begin 5-10 days after delivery. Mortality 30%. These babies may be given VZIG prophylactically within 72 hours of exposure. Acyclovir safety and dose is not established in newborns

When in-utero transmission occurs before the peripartum period there is no clinical impact in most cases.

Congenital varicella infection

C. POST- NATAL VARICELLA:
  

Usually a mild disease. Rarely severe disseminated disease occurs in newborns exposed shortly after birth. Treatment with acyclovir may be beneficial, the dose and safety of acyclovir in treating neonatal vzv, however, is not established. Breast feeding is deferred during the period of time in which the mother is likely to be viremic and/or infectious. Isolate the infant from the mother during this period.

HEPATITIS
HEPATITIS A: No horizontal transmission. HEPATITIS B: Can be acquired in-utero and perinatally.  Most infections are asymptomatic .  Symptomatic infants have jaundice and HSM.  Management of newborns depends on mother’s serology:

Infants born to HBsAg - positive mothers: Give HBIG ( 0.5ml ) and 1st dose of hepatitis B vaccine immediately after birth.  Infants born to HBsAg - negative mothers: Give hepatitis B vaccine within 2 months after birth.  Infants born to mothers whose HBsAg is unknown: Give 1st dose of vaccine within 12-hours of birth, determine Mother’s serology ….etc.

HEPATITIS C:
  

Vertical transmission is rare ( 5% ). Mode of transmission unknown. Horizontal transmission: Contaminated syringes, transfusions,...etc Infants born to HCV infected mothers have antibodies. To diagnose infection in NB do PCR.

CONGENITAL RUBELLA SYNDROME
 The risk of infection is greatest in 1st

trimester, cardiac and hearing abnormalities invariably occur  The classic CRS is characterized by: * Eye anomalies: cataracts, retinopathy, microphthalmia. * Congenital heart: PDA, P.S.

Cataracts in Congenital Rubella Syndrome

* Neurological: meningoencephalitis, EEG abnormalities, psychomotor retardation. * Sensorineural hearing loss. * Hematological: HSM, purpura. * Radiological: bone lucencies.

Some of these anomalies may not show until months or years later.

Management of recognized or suspected maternal exposure to rubella The best is to determine rubella specific IgG at the 1st obstetric visit.  If the mother is known to be seropositive:

If the mother is a known seronegative: If the maternal immune status is unknown.

Toxoplasma gondii
  

An obligate intracellular parasite. The cat is the only definitive host. Infection in the mother does not always cause congenital disease in the baby. CONGENITAL INFECTION: Infection usually occurs after 1ry maternal infection, recurrence is extremely rare. Neonatal symptomatic disease is usually severe, and is characterized by a triad of HYDROCEPHALUS, CHORIORETINITIS and I.C. CALCIFICATIONS. The sequelae of asymptomatic disease are unpredictable.

 

1. Ingestion of tissue cysts from contaminated raw or undercooked beef, lamb, or pork. 2. Ingestion of oocysts from soil, milk, water, or vegetables 3 Inhalation of oocysts. 4. Contaminated blood transfusions organ transplants, and accidental inoculation acquired in the laboratory

Laboratory diagnosis:  Serology: * Toxoplasma specific IgG. * PCR.  CBC : leucocytosis or leucopenia, lymphopenia, monocytosis, eosinophilia (30%), thrombocytopenia.  Others: ABR. Treatment: Mother: Newborn:

Erythrovirus ( Parvovirus 19 )
 A common viral infection causing the slapped cheek syndrome; fifth disease.  Has been implicated in 10% of cases of fetal non-immune hydrops fetalis.  A small percentage of susceptible women exposed to the virus are infected.

fifth disease

 Perinatal and intrapartum infections are very

rare.
 Inutero infections can result in fetal death,

nonimmune fetal hydrops, birth defects ( eyes, CNS ) and prematurity,

Diagnosis:
Serum IgM & IgG:  Absent IgG antibodies in mother rules out infection.

IgM appears by day 3 after infection and persists for 3 months at least.

Enteroviruses: HIV: Listeria: Group B streptococci:

PREVENTION
Pregnant women SHOULD AVOID :
1- Contact with ill people. 2- Eating raw or undercooked meat. 3- Contact with cat feces. 4- Sexual contact with partner infected with genital

herpes or HIV.

Human immune serum globulin can be
given to seronegative mothers exposed to: rubella, varicella, measles or hepatitis A virus. However, their role is not definite.

Treatment of women with positive culture for GBS during labor and delivery.

 Treat eyes of newborns with erythromycin

to prevent ophthalmia neonatorum.

Immunization for Rubella, Hepatitis and VZV before pregnancy if they are seronegative. Live viral vaccines should be given 3-6 months before conception. No Live Viral Vaccine should be given to pregnant women for fear of causing congenital infection.

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