Download Intrauterine infections

Chair of pediatrics with the medical
genetics
LECTURE SUBJECT:
“Intrauterine
infections”
Definition
Intrauterine infections (IUI) are an established
fact of the virus or microorganism entry to the
fetus from mother, it has clinical and laboratory
signs of infection disease.
Among the IUI the most frequent is
TORCH-infection, that means T-Toxoplasmosis,
R-Rubeola, C–Cytomegalia, H–Herpetica
infectio, O–Other.
Intrauterine contamination is a possible fact of
the entry to the fetus of various causative agents,
but there is no clinical manifestations.
Actuality


During last decades IUI take the I-III place at the
structure of mortality reasons (2-65%) of the
newborns in Ukraine.
During last years the increase of frequency of this
pathology is observed. This is caused by increase
of contamination by the IUI specific agents of
women of childbearing age (at pregnant women
cytomegalovirus is determined at 13-91% of cases,
Coxsackie enterovirus В-at 2-74%, herpes virus of
the 2 type – at 7-47%, chlamydias – at 25-40%,
mycoplasmas –at17-50%, streptococcus of the В
group – at 35%). The frequency of the fetus
infection is 5-70%.
Risk factor of the IUI beginnings






From the mother’s side:

Compromised obstetric history
(abortions, stillbirth, miscarriage of the
previous pregnancies)
Pathologic course of present pregnancy 
(threat of abortion, hydramnion,
exfoliation of placenta, untimely
discharge of amniotic fluid, gestosis)

Diseases of the urogenital system
(colpitis, vulvovaginitis, pyelonephritis,

cervical erosion, ovarian cysts)
Extragenital pathology of pregnancy,

ARVI during pregnancy
Pathologic course of delivery
(protracted waterless interval, dirty
amniotic fluid, obstetric help at birth) 

Inflammatory infectious processes,
increase of t of mother before, during or
after birth (endometritis, mastitis)

From the child’s side:
Prematurity, intrauterine growth
retardation ,growth violations,
disembriogenetic stigma
Manifestations of the nonspecific
infectious process (pneumonia ,
hepatitis, meningoencephalitis, fever at
the 1st day of life)
Manifestations of the specific infectious
process
Inflammatory changes of the
peripheral blood
Typical changes at USE of brain
(hemorrhages, ventriculitis, echodense
inclusions, internal hydrocephalus)
Jaundice of the unknown origin
Micro- or hydrocephalus, lasting
convulsions
Neurologic violations, that are first time
registered in few days after birth
Etiology
Viruses:
cytomegalovirus – DNA-virus from the group of herpetic infection;
of herpes simplex of the 1st – 2nd type – DNA-virus from the group of
herpetic infection;
of chickenpox - DNA-virus from the group of herpetic infection;
of rubella, measles, epidemic parotiditis – RNA-virus, mixovirus;
enterovirus – RNA-virus from the group of Coxsackie, ЕСНО;
respiratory viruses – of grippe, paragrippe, adenoviruses, RS-viruses;
of viral hepatitis.

Bacteria: listeria, treponema, mycobacteria Kochii, opportunistic
pathogenic flora (streptococcus B, D, Escherichia coli,
enterobacteria).

Parasites – toxoplasma.

Mycoplasma.

Chlamidia.

IUI characteristic features
Source of infection (pregnant woman, parturient woman, mother)
 Infection ways:
Contaminational – it occurs through infected amniotic fluid by:
Hematogenic (diaplacental) - placenta injure, placental barrier violations.
ascending way – in case of infection entry from vagina, neck of uterus;
descending way – in case of infection entry from abdominal cavity through uterine tubes;
contacting – in case of localization of the infection source right in the uterine wall, in the
placenta.
Intranatal – during fetus going through infected maternal passages.
 IUI causative agents have the high tropism to the majority of fetus tissues and organs.
 The diagnostics is difficult because of:
The infection process in the mother’s organism often is symptomless;
The fetus disease is caused not only by the direct action of causative agent, but also by
mixed infection, intoxication, immunologic changes, metabolism violations at mother’s
organism;
This pathology often is hidden by the mask of intrauterine growth retardation, hypoxia, birth
trauma
 IUI of the newborns often is displayed by latent infection because of prolonged agent
persistence.
 The level of injury depends on ruggedness of contagion and the terms of gestation.
 The possibility of fetus infection increases with increase of gestation terms.

Pathogenesis



The fetus infection during the embryonal growth period causes
the development of infection embryopathies, that displays as
fetus wastage at the early terms, stillbirth, development of the
congenital growth defects (as a result of alternative,
proliferative inflammatory changes).
The fetus infection during placental growth period causes the
fetopathies development. In this case placenta and fetus have
the pathogenic changes. The fetopathies include: preterm
delivery, intrauterine growth retardation, plural stigmas. The
development of congenital defects of the systems that did not
finish its growth is possible. Till the 5th- 6th month of antenatal
growth the disease courses as generalized process with the
blood circulation violations, dystrophic and necrotic changes.
The infection during the 3rd trimester of pregnancy causes the
child’s birth with the disease manifestations. Pathologic
changes are caused by the ternary inflammation character.
IUI consequences
І. At antenatal infection:
Abortions, miscarriages, stillbirth.
Growth defects, dysplasia of the internals.
Neonatal death.
Recovery.
Persistence of the causative agent of the clinically healthy
child.
ІІ. At intranatal infection:
Growth imbalance.
Functional and organic violations (encephalopathies,
endocrinopathy).
Chronic diseases (nephritis, pyelonephritis, pneumonia).
Classification
By the periods of initiation:
antenatal (embryopathies, fetopathies)
intranatal
postnatal (nosocomial)
 By the periods:
early neonatal ( from the birth till the 7th
day)
late neonatal (8-28 days)
 By the transfer path:
hematogenic
contaminational
intranatal
 By the etiology: viral, bacterial,
parasitic, mycoplasmal, chlamidial,
fungous, mixed

By the form:
localized
generalized
 By the phase:
active
inactive
residual
 By the course:
acute
subacute
chronic
latent

DIAGNOSIS EXAMPLES: Intrauterine infection, intranatal herpetic infection of the II
type, localized skin form, active phase, acute course.
Clinical syndromes of the infection process at
newborns






Intoxicational (decrease of appetite, weight increase delay, hypotrophy,
flaccidity, sclerema, bleach, grey color of skin or jaundice, purpura).
Respiratory (dyspnea, tachypnea, apnea, cyanosis of the nasolabial
triangle, the ancillary muscles part in the breathing act).
Dyspeptic (regurgitation, vomiting, stomach bloating, frequent fluid stool,
sponginess of the front abdominal wall, liver and spleen increase).
Cardiovascular (tachycardia, relief of the heart sounds, broadening of the
heart borders, paleness, mottled skin, cold limbs, edema, sponginess, AP
decrease).
Nervous system injury (flaccidity, adynamia or excitation, convulsions,
brain scream, bulging of the large fontanel, muscular hypotension,
hyporeflexia).
Hematologic violations (anemia, trobocytopenia, leucopenia or
leukocytosis, raised hemorrhage, splenomegaly).
Diagnostics
Anamnesis (accounting all the risk factors).

Clinical presentation

Laboratory data, subsidiary research methods data:
Transabdominal amniocentesis (indification of the infection agent, glucose level
determination, C-reactive protein, correlation of the amount of stab granulocytes
and the total leukocytes content, the part of haptoglobulins);
Cordocentesis (the agent determination or the level of specific antibodies in the
umbilical blood);
Bacteriologic and viral researches of the cervical canal of urethra, vagina);
Serologic methods (level of specific antibodies in the women’s blood);
Ultrasonic scanning (the next features mean the fetus infection: disparity of the head
size to the pregnancy period, intrauterine growth retardation, calcifications in the
liver, kidneys, brain ventricles, placenta, hydramnion, violation of the structure
and placenta development).
Cardiotocography;
Hystologic research of placenta;
IFA, PCR, DNA- hybridization.

The inspections complex at the IUI
suspicion
Amniotic fluid research:
bacteriologic research (diagnostic criteria is the presence of 103 microbal units of the
opportunistic group in 1ml of fluid)
cytological research of sediment (5 and > leukocytes is high level of ANI development)

Vagina content research (bacteriologic and bacterioscopic).

Placenta analysis (bacteriologic, virological, histological).

General blood analysis with accounting of thrombocytes (anemia,
thrombocytopenia, leucopenia, raised ESR, leukocytosis with the lymphocytosis,
monocytosis, shift of the formula to the left).

Biochemical analysis of blood (total protein content, protein fraction decrease,
presence of C-reactive protein, increased activity of transaminases).

Bacteriologic research of blood, stomach content, stool, urine, liquor.

General urine analysis.

Roentgenologic research of internal organs of chest, skull.

Neurosonography.

Immunologic research of the umbilical blood (decrease of Ig G and increase of Ig
M, Ig A, alpha-fetoprotein level).

Serologic analysis in dynamics.

General treatment methods
-
-
-
-At the viral IUI (herpes, CMV) – specific
antiviral preparations (vidarabin, virazol, virolex,
acyclovir);
-At bacterial and parasitogenic ANI (lysteriosis,
congenital syphilis, toxoplasmosis, chlamidiosis,
mycoplasmosis) – specific antibacterial therapy
-Pathogenic methods of immunotherapy
(immunoglobulin, interferon, laferon).
Clinical and diagnostic criteria of
cytomegalovirus infection
Causative agent: cytomegalovirus – DNA- virus of the herpetic origin. It has some features:
immensely large DNA, the possibility of replication without cell damage, slow replication,
it causes the rapid decrease of the cell immunity, the viral excretion survives during 2-8
years.
Source: mother, also biologic fluids and discharge.
The infection path: transplacental, intranatal, during feeding with the breast milk, during
hemotransfusions.
For the generalized form of CMV-infection is characteristic the following: prematurity,
intrauterine growth retardation, hepatosplenomegaly, jaundice, nervous system injury,
interstitial pneumonia, damage of salivary glands, eyes, internal ear, kidney, hemorrhagic
syndrome.
The localized form (hepatitis) is much more rear.
The tetrad is characteristic: jaundice, hepatosplenomegaly, thrombocytopenia, hard damage of
the nervous system.
Laboratory diagnostics: cystoscopic, virological methods, IFA, PCR, DNA- hybridization.
Treatment: cytotect by 2ml/kg every 2 days or 4 ml/kg every 4 days intravenously till the
decrease of clinical symptoms; phoscarnet by 180ml/kg in 5 doses intravenously during 1421 days. Sustentacular dose is 90 ml/kg/day. Gancyclovir (cymeven) by 5 mg/kg 2 times a
day intravenously during 14-21 days; laferon by 100 000 UA intravenously 1 time a day
during 10 days.
Clinical and diagnostic criteria of
herpetic infection
Causative agent: herpes simplex virus, DNA- virus of the herpetic origin (in
90% of cases – II type), that has some features: persistence in the CNS,
support of latent infection.
Source: mother.
The infection path: intranatal (85 % of cases), transplacental (in case of
viremia of mother), contaminational (ascending way).
Clinically the disease is presented as generalized forms (lethality without
treatment is 90%) and localized forms (with the mostly defeat of CNS –
lethality without treatment is 50%, with the mostly injury of skin and
mucous - lethality without treatment is 18%).
Laboratory diagnostics: virological method, IEA, PLR, DNA-hybridization,
histological research of placenta.
Treatment: acyclovir (zovirax, virolex) by 30mg/kg/day in 3 doses
intravenously during 2-3 weeks, vidarabin 15-30 mg/kg/day intravenously
droply in 2 doses during 10-14 days, laferon by 100 000 UA intravenously
1 time a day during 10 days.
Clinical and diagnostic criteria of
listeriosis
Causative agent - Listeria monocytogenesis- gram-positive bacillus.
Source: mother.
The infection path: transplacental
Diagnostics:
-In the anamnesis- contact with the pets, increase of body t during pregnancy, fever,
pielitis phenomena, spontaneous abortions.
-Dirty amniotic fluid.
-Child’s clinical presentation – increase of body t, RDS, convulsions, papular petechial skin, mucous rash, inflectional granuloma at the tonsils, back pharynx
wall, conjunctiva.
-Radiologicaly – plural, dense infiltrative shadows, that is similar to military
tuberculosis presentation.
-Specific research methods- bacteriological research of the amniotic fluid,
placenta, liquor, blood; histological placenta research; serological research
(increase of antibodies titer in 4 times and more has the diagnostics value).
Treatment: ampicillin by 200 mg/kg/day, gentamicin by 7 mg/kg/day during 14
weeks
Clinical and diagnostic criteria of congenital
syphilis
Causative agent: Treponema pallidum
Source: mather.
The infection path: transplacental, intranatal
Typical clinical triad for congenital syphilis:
-Syphilitic pemphigus with tissue induration.
-Syphilitic rhinitis.
- Hepatosplenomegaly.
Also it can be syphilitic chorioretinitis, generalized lymphoepitheliopathy, syphilitic osteochondritis,
periostitis, serous meningitis, anemia, thrombocytopenia, monocytosis, intrauterine growth
retardation, gerontal child’s look.
Diagnostics:
-Microscopy in the dark field of view – agent discharge from vesicles, nose discharges, liquor.
-Serological child’s and mother’s research (RV, RIF, RIT – results are significant after the 10th day of
child’s life);
-Hystological placenta research.
-Radiological research of flat skull bones and long tubular bones of the upper limbs.
-Research of the eye bottom.
-Examination by otalaryngologist, neurologist.
-Neurosonography, US- research of the organs of chest.
Treatment: penicillin by 200 000/kg/day in 6 doses during 28 days.
Preventive measures: three times obligatory serologic research of blood of pregnant women, the last one –
not late than 36 weeks of pregnancy.
Clinical and diagnostic criteria of toxoplasmosis
Causative agent: Toxoplasma gondi – intracellular parasite, that is protozoan.
Source: mother.
The infection path: transplacental.
For the congenital toxoplasmosis the following triad is typical:
-Hydro- and microcephalus;
-convulsions;
-chorioretinitis;
-calcification in the brain.
Generalized form is characterized by intoxication, hepatosplenomegaly with jaundice, hemorrhagic
syndrome, skin rash, liquor changes, pneumonia development, myocarditis, nephritis, hematologic
violations.
Diagnostics:
-secretion of the causative agent from liquor, blood, placenta, brain tissues.
-IEA;
-Reaction with methylene blue;
-Skin test with toxoplasmin (reaction is positive if diameter is more than 10mm).
-Histological placenta research;
-Roentgenography of skull;
-Reurosonography.
-Consultation of oculist, neurologist.
Treatment: sulfadimesin by 100mg/kg/day in 2 doses + chloridin (pyrimethamin by 2mg/kg/day in the
first 2 days, then by 1mg/kg/day during 6 month and 3 times a week during 12 month; spyramycin
(rovamycin) by 100 mg/kg/day in 2 doses during 1 month (4 courses per year); in case of expressed
inflammatory process – prednizolon by 2 mg/kg/day.
Clinical and diagnostic criteria of chlamidia infection
Causative agent: Chlamidia trachomatis – obligate intracellular
parasite, it occupies a middle place between bacteria and viruses.
Source: mother.
The infection path: ante- and intranatal.
Clinical forms:
-Generalized infection with injury of lungs, heart, liver;
-Meningoencephalitis;
-Antenatal pneumonia;
-Syndrome of breathing violations;
-gastroenteropathy;
-conjunctivitis.
Clinical and diagnostic criteria of chlamidia infection
Diagnostics:
-anamnesis;
-clinical presentation;
-laboratory and instrumental research methods:
total blood analysis – moderate anemia, eosinophilia > 7%, monocytosis >10%;
microbiological examination of mother and child;
method of direct immunofluorescence;
immunoenzyme method (ELISA);
PLR, DNA- hybridization;
Cultural method;
Placenta research.
Treatment: erythromycin by 40 mg/kg/ day per os during 21 days. Chlamidia
persistence can save during the first year of child’s life at 60% of newborns.
Sumamed at the first day by 10 mg/kg per os, than during 7 days by 5 mg/kg/day. It
provides total agents elimination from the organism.
Clacyd by 10 mg/kg/day in 2 doses during 14 days intramuscularly or intravenously.
Preventive measures
Providing of microbiological health of women and men of
reproductive age
Pregnancy planning, conscious attitude to a child’s birth
Usage and introducing of the modern methods of early
diagnostics of ANI of fetus and pregnant women of the risk
group
Introducing of modern perinatal techniques of helping mothers
and newborns
Microbiological monitoring in the ITAR departments for
controlling circulation of hospital viral, fungus, bacteria strains
Limited manipulations holding, that presuppose contact with
medical staff and equipment
Breast feeding, rooming-in of mother with newborn
Thank You for attention!