Endometritis: MedlinePlus Medical Encyclopedia

URL of this page: //medlineplus.gov/ency/article/001484.htm

To use the sharing features on this page, please enable JavaScript.

Endometritis is an inflammation or irritation of the lining of the uterus (the endometrium). It is not the same as endometriosis.

Endometritis is caused by an infection in the uterus. It can be due to chlamydia, gonorrhea, tuberculosis, or a mix of normal vaginal bacteria. It is more likely to occur after miscarriage or childbirth. It is also more common after a long labor or C-section.

The risk for endometritis is higher after having a pelvic procedure that is done through the cervix. Such procedures include:

• D and C (dilation and curettage)
• Endometrial biopsy
• Hysteroscopy
• Placement of an intrauterine device (IUD)
• Childbirth (more common after C-section than vaginal birth)

Endometritis can occur at the same time as other pelvic infections.

Symptoms may include:

• Swelling of the abdomen
• Abnormal vaginal bleeding or discharge
• Discomfort with bowel movement (including constipation)
• Fever
• General discomfort, uneasiness, or ill feeling
• Pain in lower abdomen or pelvic region (uterine pain)

The health care provider will perform a physical exam with a pelvic exam. Your uterus and cervix may be tender and the provider may not hear bowel sounds. You may have cervical discharge.

The following tests may be performed:

• Cultures from the cervix for chlamydia, gonorrhea, and other organisms
• Endometrial biopsy
• ESR (erythrocyte sedimentation rate)
• Laparoscopy
• WBC (white blood count)
• Wet prep (microscopic exam of any discharge)

You will need to take antibiotics to treat the infection and prevent complications. Finish all your medicine if you have been given antibiotics after a pelvic procedure. Also, go to all follow-up visits with your provider.

You may need to be treated in the hospital if your symptoms are severe or occur after childbirth.

Other treatments may involve:

• Fluids through a vein (by IV)
• Rest

Sexual partners may need to be treated if the condition is caused by a sexually transmitted infection (STI).

In most cases, the condition goes away with antibiotics. Untreated endometritis can lead to more serious infections and complications. Rarely, it may be associated with a diagnosis of endometrial cancer.

Complications may include:

• Infertility
• Pelvic peritonitis (generalized pelvic infection)
• Pelvic or uterine abscess formation
• Septicemia
• Septic shock

Call your provider if you have symptoms of endometritis.

Call right away if symptoms occur after:

• Childbirth
• Miscarriage
• Abortion
• IUD placement
• Surgery involving the uterus

Endometritis may be caused by STIs. To help prevent endometritis from STIs:

• Treat STIs early.
• Make sure sexual partners are treated in the case of a STI.
• Follow safer sex practices, such as using condoms.

Women having a C-section may have antibiotics before the procedure to prevent infections.

• Pelvic laparoscopy
• Endometritis

Centers for Disease Control and Prevention website. Sexually transmitted infections treatment guidelines, 2021. www.cdc.gov/std/treatment-guidelines/default.htm. Updated July 22, 2021. Accessed August 31, 2021.

Duff WP. Maternal and perinatal infection in pregnancy: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al, eds. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Philadelphia, PA: Elsevier; 2021:chap 58.

Eckert LO, Lentz GM. Genital tract infections: vulva, vagina, cervix, toxic shock syndrome, endometritis, and salpingitis. In: Gershenson DM, Lentz GM, Valea FA, Lobo RA, eds. Comprehensive Gynecology. 8th ed. Philadelphia, PA: Elsevier; 2022:chap 23.

Updated by: John D. Jacobson, MD, Department of Obstetrics and Gynecology, Loma Linda University School of Medicine, Loma Linda, CA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

Endometritis: Symptoms, causes, and treatment

Endometritis is inflammation of the inner lining of the uterus. It can lead to abdominal pain and bleeding, but there may be no symptoms. It is different from endometriosis, where endomentrial-type tissue grows outside the uterus.

Endometritis is different from endometriosis, though both conditions affect the lining of the uterus, also called the endometrium. Another related condition is endomyometritis, where inflammation happens in the middle layer of the uterus, called the myometrium.

This article provides an overview of endometritis, including its causes, symptoms, diagnosis, and possible complications. We also look at the relationship between endometritis and fertility.

Endometritis does not always cause symptoms, and some people may be unaware they have it. If symptoms do occur, they can include:

• pelvic or abdominal pain
• vaginal bleeding or unusual vaginal discharge
• fever or chills
• feeling unwell or extremely fatigued
• constipation or pain when going to the bathroom

Endometritis is also associated with infertility and pregnancy loss.

Anyone who experiences one or more of these symptoms should contact their doctor to find out the cause.

Endometritis occurs as a result of an infection in the lining of the uterus, known as the endometrium. Such infections may develop due to abnormal bacteria, or bacteria usually found in the vagina.

The cervix is the opening to the uterus, and it usually keeps bacteria out of the uterus. However, bacteria can get in when the cervix is open. This may happen for various reasons, such as during childbirth or surgery.

Possible risk factors for endometritis include:

• Childbirth or pregnancy loss: These are the most common causes of inflammation of the endometrium.
• Cesarean delivery: Endometritis is more common after a cesarean section than a vaginal delivery and after an unscheduled versus a scheduled cesarean.
• Sexually transmitted infections (STIs) and other bacteria: People can pass on STIs, including chlamydia and gonorrhea, during sexual activity. An STI can cause an infection in the endometrium, so it is important to practice safe sex.
• Bacteria in the uterus: Bacteria normally present in the vagina and cervix can cause endometritis if they enter the uterus.
• Pelvic procedures: Some procedures can let bacteria into the uterus, especially those that involve accessing internal organs and tissues via the cervix or uterus. Examples include:
  • dilation and curettage, which involves removing tissue from the inside of the uterus
  • endometrial biopsy, which involves taking a tissue sample of the endometrium
  • hysteroscopy, which is when a doctor inserts a small telescope into the uterus to look for abnormalities
  • intrauterine device insertion
  • cesarean section
• Pelvic inflammatory disease (PID): PID is an infection in the pelvis that is often associated with endometritis. Without swift medical treatment, PID can become serious.

Endometritis is different from endometriosis, though both conditions affect the lining of the uterus.

Endometritis is when the lining of the uterus becomes inflamed due to an infection. Endometriosis is where tissue similar to the lining of the uterus grows outside the uterus. An infection does not cause endometriosis.

The symptoms of endometriosis vary from one person to another but typically include:

• pain in the lower abdomen or back, which usually worsens during a period
• experiencing one or more of the following symptoms during a period:
  • severe period pain
  • pain when urinating or when having a bowel movement
  • blood in the urine
  • nausea
  • diarrhea
  • constipation
• pain during or after sex
• difficulty getting pregnant

There is currently no cure for endometriosis, though treatments are available to help alleviate the symptoms.

Polycystic ovarian syndrome (PCOS) is a condition that affects how a person’s ovaries function. The condition relates to hormonal imbalances in the body. Unlike endometritis, PCOS does not occur due to infection.

Experts do not know the exact cause of PCOS. However, the condition likely has a genetic link since it often runs in families.

In order to receive a diagnosis of PCOS, a person must experience two or more of the following:

• Irregular periods: This indicates that the ovaries are not regularly releasing eggs.
• Excess androgens: Androgens are male sex hormones. Both males and females have androgens, but some people with PCOS have higher levels than usual. Excess androgens can lead to physical changes, such as excessive facial or body hair.
• Polycystic ovaries: The ovaries can become enlarged, and ultrasound shows the presence of multiple small follicles or fluid-filled cysts in the ovaries.

PCOS is difficult to diagnose because its symptoms mirror those of other conditions, such as:

• cardiovascular disease
• acne
• depression
• sleep apnea
• type 2 diabetes

There is currently no cure for PCOS, though treatments are available to help alleviate the symptoms.

Endometritis can affect a person’s ability to get pregnant or stay pregnant. Inflammation of the uterus can cause scarring, which prevents an embryo from implanting and developing normally within the uterine wall.

A 2016 review reports that chronic endometritis can affect fertility by stopping the fertilized egg from implanting into the uterus lining and increasing the likelihood of repeated pregnancy loss.

However, the same study reports that antibiotic treatment can lead to a significant improvement in fertility and successful pregnancies.

A study from 2018 worked with 95 females who had fertility issues. They found that over half of the participants had chronic endometritis and that antibiotic therapy improved their symptoms by more than 80%. With successful treatment, they had increased pregnancy and childbirth rates.

Fertility specialists sometimes suggest that people receive testing or treatment for endometritis, especially in cases of repeated pregnancy loss or multiple unsuccessful in vitro fertilization cycles involving embryos of good quality.

When diagnosing endometritis, a doctor will start by taking a medical history and performing a physical exam. The latter will likely involve a pelvic exam to evaluate the internal reproductive organs. The doctor will look for tenderness in the uterus and possible discharge from the cervix.

A doctor may carry out the following tests to rule out other possible causes of the symptoms:

• Blood testing: A complete blood count can help identify signs of infection or inflammation.
• Cervical cultures: The doctor may take a swab from the cervix to look for chlamydia, gonorrhea, or other bacteria.
• Wet mount: The doctor may collect discharge from the cervix and analyze it under a microscope. This can help to identify other causes of infection or inflammation.
• Endometrial biopsy: This procedure involves dilating the cervix to allow a small instrument or pipelle into the uterus. The instrument takes a small sample of tissue, and a doctor sends the sample off to the lab for analysis. It is a brief procedure that can take place in a doctor’s office.
• Laparoscopy or hysteroscopy: These procedures involve the use of a scope, which is a tiny camera attached to a thin, flexible tube. This allows a doctor to look directly inside the uterus.

A person should contact a doctor anytime they experience pelvic pain or discomfort or unusual discharge or bleeding. Some pelvic infections can cause serious complications, so it is important to start treatment quickly.

Treatment for endometritis aims to eliminate the infection and resolve inflammation of the uterus. Treatment will also prevent any further complications. This may involve the following:

• Antibiotics: These medications fight the bacteria causing inflammation of the uterine lining. If the infection is very severe, a person may require intravenous antibiotics in the hospital.
• Treating sexual partners: If the endometritis is due to an STI, the person’s sexual partner or partners may also require antibiotic treatment.
• Further tests: A person may require cervical cultures or an endometrial biopsy to ensure that the infection is completely gone after finishing the course of antibiotics. If the infection remains, a doctor may recommend a different antibiotic.
• Surgery to remove tissue: A surgeon may need to remove any tissue left inside the uterus following childbirth or pregnancy loss.
• Treating any abscesses: In some cases, the infection may cause an abscess within the abdomen. A person may then require surgery or a needle aspiration to remove infected fluid or pus from the abscess.

People who are at risk of developing endometritis should receive information from their doctor or nurse about the signs and symptoms to look out for. This includes people who have recently given birth and those who have recently undergone a pelvic examination or procedure.

A doctor may prescribe antibiotics to help prevent endometritis in situations where a person is at risk of developing the condition, such as when undergoing a scheduled pelvic procedure or surgery. A doctor may prescribe the antibiotics prior to or immediately following the procedure.

Because STIs can also cause endometritis, it is crucial that people maintain their sexual health, especially with nonmonogamous partners. Behaviors that can help include attending regular screenings for STIs and consistently using barrier contraception, such as condoms.

Without treatment, endometritis may cause the following complications:

• infertility
• pelvic peritonitis, which is a general pelvic infection
• abscess in the pelvis or uterus
• septicemia, which is bacteria in the bloodstream
• septic shock, which is severe and potentially life threatening low blood pressure due to septicemia

The outlook for a person with endometritis is very good, especially if they receive antibiotic treatment.

Getting a prompt diagnosis and appropriate treatment significantly reduces the risk of complications.

Intrauterine infections. What are Intrauterine Infections?

IMPORTANT
The information in this section should not be used for self-diagnosis or self-treatment. In case of pain or other exacerbation of the disease, only the attending physician should prescribe diagnostic tests. For diagnosis and proper treatment, you should contact your doctor.

Intrauterine infections are a group of diseases of the fetus and newborn that develop as a result of infection in the prenatal period or during childbirth. Intrauterine infections can lead to fetal death, spontaneous abortion, intrauterine growth retardation, premature birth, the formation of congenital malformations, damage to internal organs and the central nervous system. Methods for diagnosing intrauterine infections include microscopic, cultural, enzyme immunoassay, molecular biological studies. Treatment of intrauterine infections is carried out using immunoglobulins, immunomodulators, antiviral, antibacterial drugs.

• Causes of intrauterine infections
• Classification
• Symptoms of intrauterine infections
  • Congenital toxoplasmosis
  • Congenital rubella
  • Congenital cytomegaly
  • Congenital herpes infection
• Diagnostics
• Treatment of intrauterine infections
• Prognosis and prevention
• Prices for treatment

General

Intrauterine infections are pathological processes and diseases caused by antenatal and intranatal infection of the fetus. The true prevalence of intrauterine infections has not been established, however, according to generalized data, at least 10% of newborns are born with congenital infections. The relevance of the problem of intrauterine infections in pediatrics is due to high reproductive losses, early neonatal morbidity, leading to disability and postnatal death of children. The issues of prevention of intrauterine infections lie in the plane of consideration of obstetrics and gynecology, neonatology, and pediatrics.

Intrauterine infections

Causes of intrauterine infections

Intrauterine infections develop as a result of infection of the fetus in the prenatal period or directly during childbirth. Usually, the source of intrauterine infection for a child is the mother, i.e., there is a vertical transmission mechanism, which in the antenatal period is realized by transplacental or ascending (through infected amniotic fluid) routes, and in the intrapartum by aspiration or contact routes.

Less commonly, iatrogenic infection of the fetus occurs during pregnancy when a woman undergoes invasive prenatal diagnostics (amniocentesis, cordocentesis, chorionic villus biopsy), administration of blood products to the fetus through the vessels of the umbilical cord (plasma, erythrocyte mass, immunoglobulins), etc.

In the antenatal period, infection of the fetus is usually associated with viral agents (rubella, herpes, cytomegaly, hepatitis B and C, Coxsackie, HIV) and intracellular pathogens (toxoplasmosis, mycoplasmosis).

In the intranatal period, microbial contamination occurs more often, the nature and degree of which depends on the microbial landscape of the mother’s birth canal. Among bacterial agents, the most common are enterobacteria, group B streptococci, gonococci, Pseudomonas aeruginosa, Proteus, Klebsiella, etc. The placental barrier is impermeable to most bacteria and protozoa, however, if the placenta is damaged and placental insufficiency develops, antenatal microbial infection can occur (for example, by the causative agent of syphilis). In addition, intranatal viral infection is not excluded.

Factors in the occurrence of intrauterine infections are a burdened obstetric and gynecological history of the mother (nonspecific colpitis, endocervicitis, STDs, salpingo-oophoritis), an unfavorable course of pregnancy (threat of interruption, gestosis, premature detachment of the placenta) and infectious morbidity of the pregnant woman. The risk of developing a manifest form of intrauterine infection is significantly higher in premature babies and in the case when a woman becomes infected primarily during pregnancy.

The severity of clinical manifestations of intrauterine infection is affected by the timing of infection and the type of pathogen. So, if infection occurs in the first 8-10 weeks of embryogenesis, pregnancy usually ends in spontaneous miscarriage. Intrauterine infections that occur in the early fetal period (up to 12 weeks of gestation) can lead to stillbirth or the formation of gross malformations. Intrauterine infection of the fetus in the II and III trimester of pregnancy is manifested by damage to individual organs (myocarditis, hepatitis, meningitis, meningoencephalitis) or a generalized infection.

It is known that the severity of the manifestations of the infectious process in a pregnant woman and in a fetus may not coincide. The asymptomatic or oligosymptomatic course of infection in the mother can cause severe damage to the fetus, up to his death. This is due to the increased tropism of viral and microbial pathogens for embryonic tissues, mainly the central nervous system, heart, and organ of vision.

Classification

The etiological structure of intrauterine infections involves their division into:

• viral (viral hepatitis, herpes, rubella, SARS, cytomegaly, mumps, enterovirus infection)
• bacterial (tuberculosis, syphilis, listeriosis, sepsis)
• parasitic and fungal (mycoplasmosis, toxoplasmosis, chlamydia, candidiasis, etc.)

To designate a group of the most common intrauterine infections, the abbreviation TORCH syndrome is used, which combines toxoplasmosis (toxoplasmosis), rubella (rubella), cytomegalovirus (cytomegalovirus), herpes (herpes simplex). The letter O (other) denotes other infections, including viral hepatitis, HIV infection, chicken pox, listeriosis, mycoplasmosis, syphilis, chlamydia, etc.).

Symptoms of intrauterine infections

The presence of intrauterine infection in a newborn may be suspected already during childbirth. In favor of intrauterine infection, the outflow of turbid amniotic fluid contaminated with meconium and having an unpleasant odor, the state of the placenta (plethora, microthroboses, micronecrosis) may indicate. Children with intrauterine infection are often born in a state of asphyxia, with prenatal hypotrophy, enlarged liver, malformations or stigmas of disembryogenesis, microcephaly, hydrocephalus. From the first days of life, they have jaundice, elements of pyoderma, roseolous or vesicular skin rashes, fever, convulsive syndrome, respiratory and cardiovascular disorders.

The early neonatal period with intrauterine infections is often aggravated by interstitial pneumonia, omphalitis, myocarditis or carditis, anemia, keratoconjunctivitis, chorioretinitis, hemorrhagic syndrome, etc. Instrumental examination of newborns can reveal congenital cataracts, glaucoma, congenital heart defects, cysts and brain calcifications.

In the perinatal period, the child has frequent and profuse regurgitation, muscle hypotension, CNS depression syndrome, and gray skin. In the later stages, with a long incubation period of intrauterine infection, the development of late meningitis, encephalitis, and osteomyelitis is possible.

Consider the manifestations of the main intrauterine infections that make up the TORCH syndrome.

Congenital toxoplasmosis

Intrauterine infection with the unicellular protozoan parasite Toxoplasma Gondii leads to severe fetal damage – developmental delay, congenital malformations of the brain, eyes, heart, and skeleton.

After birth in the acute period, intrauterine infection is manifested by fever, jaundice, edematous syndrome, exanthema, hemorrhages, diarrhea, convulsions, hepatosplenomegaly, myocarditis, nephritis, pneumonia. In subacute course, signs of meningitis or encephalitis dominate. With chronic persistence, hydrocephalus with microcephaly, iridocyclitis, strabismus, and atrophy of the optic nerves develop. Sometimes there are monosymptomatic and latent forms of intrauterine infection.

Late complications of congenital toxoplasmosis include oligophrenia, epilepsy, and blindness.

Congenital rubella

Intrauterine infection occurs due to rubella during pregnancy. The likelihood and consequences of infection of the fetus depend on the gestational age: in the first 8 weeks, the risk reaches 80%; The consequences of intrauterine infection can be spontaneous abortion, embryo- and fetopathy. In the II trimester, the risk of intrauterine infection is 10-20%, in the III – 3-8%.

Babies with intrauterine infection are usually born prematurely or with low birth weight. The neonatal period is characterized by hemorrhagic rash, prolonged jaundice.

The classic manifestations of congenital rubella are represented by Greg’s triad: eye damage (microphthalmia, cataract, glaucoma, chorioretinitis), CHD (open ductus arteriosus, ASD, VSD, pulmonary artery stenosis), damage to the auditory nerve (sensoneural deafness). In the case of intrauterine infection in the second half of pregnancy, the child usually has retinopathy and deafness.

In addition to the main manifestations of congenital rubella, other anomalies may also be detected in a child: microcephaly, hydrocephalus, cleft palate, hepatitis, hepatosplenomegaly, malformations of the genitourinary system and skeleton. In the future, intrauterine infection reminds of itself by the child’s lag in physical development, mental retardation or mental retardation.

Congenital cytomegaly

Intrauterine infection with cytomegalovirus infection can lead to local or generalized damage to many organs, immunodeficiency, purulent-septic complications. Congenital developmental defects usually include microcephaly, microgyria, microphthalmia, retinopathy, cataracts, congenital heart disease, etc. The neonatal period of congenital cytomegaly is complicated by jaundice, hemorrhagic syndrome, bilateral pneumonia, interstitial nephritis, and anemia.

Long-term effects of intrauterine infection include blindness, sensorineural deafness, encephalopathy, liver cirrhosis, pneumosclerosis.

Congenital herpes infection

Intrauterine herpes infection can occur in a generalized (50%), neurological (20%), mucocutaneous (20%) form.

Generalized intrauterine congenital herpes infection occurs with severe toxicosis, respiratory distress syndrome, hepatomegaly, jaundice, pneumonia, thrombocytopenia, hemorrhagic syndrome. The neurological form of congenital herpes is clinically manifested by encephalitis and meningoencephalitis. Intrauterine herpes infection with the development of skin syndrome is accompanied by the appearance of a vesicular rash on the skin and mucous membranes, including internal organs. With the layering of a bacterial infection, sepsis of the newborn develops.

Intrauterine herpes infection in a child can lead to the formation of malformations – microcephaly, retinopathy, limb hypoplasia (cortical dwarfism). Among the late complications of congenital herpes are encephalopathy, deafness, blindness, psychomotor retardation.

Diagnostics

Currently, an urgent task is the prenatal diagnosis of intrauterine infections. For this purpose, in the early stages of pregnancy, smear microscopy, bacteriological culture from the vagina for flora, PCR examination of scrapings, and examination for the TORCH complex are performed. Pregnant women from the high-risk group for the development of intrauterine infection are indicated for invasive prenatal diagnosis (chorionic villus aspiration, amniocentesis with amniotic fluid examination, cordocentesis with cord blood examination).

It is possible to identify echographic markers of intrauterine infections using obstetric ultrasound. Indirect echographic signs of intrauterine infection include oligohydramnios or polyhydramnios; the presence of a hyperechoic suspension in the amniotic fluid or amniotic bands; chorionic villus hypoplasia, placentitis; premature aging of the placenta; fetal edematous syndrome (ascites, pericarditis, pleurisy), hepatosplenomegaly, calcifications and malformations of internal organs, etc. In the process of Doppler examination of blood flow, disturbances in fetal-placental blood flow are detected. Cardiotocography reveals signs of fetal hypoxia.

After the birth of a child, in order to reliably verify the etiology of intrauterine infection, microbiological (virological, bacteriological), molecular biological (DNA hybridization, PCR), serological (ELISA) examination methods are used. Histological examination of the placenta is of great diagnostic value.

According to indications, newborns with intrauterine infections on the first day of life should be examined by a pediatric neurologist, pediatric cardiologist, pediatric ophthalmologist, and other specialists. It is advisable to carry out echocardiography, neurosonography, ophthalmoscopy, hearing test using the method of evoked otoacoustic emission.

Treatment of intrauterine infections

General principles for the treatment of intrauterine infections involve immunotherapy, antiviral, antibacterial and post-syndromic therapy.

Immunotherapy includes the use of polyvalent and specific immunoglobulins, immunomodulators (interferons). Antiviral therapy of directed action is carried out mainly with acyclovir. For antimicrobial therapy of bacterial intrauterine infections, broad-spectrum antibiotics (cephalosporins, aminoglycosides, carbapenems) are used, and macrolides are used for mycoplasmal and chlamydial infections.

Posyndromic therapy of intrauterine infections is aimed at stopping individual manifestations of perinatal CNS damage, hemorrhagic syndrome, hepatitis, myocarditis, pneumonia, etc.

Prognosis and prevention

With generalized forms of intrauterine infections, mortality in the neonatal period reaches 80%. With local forms, serious lesions of internal organs occur (cardiomyopathy, COPD, interstitial nephritis, chronic hepatitis, cirrhosis, etc.). In almost all cases, intrauterine infections lead to damage to the central nervous system.

Prevention of intrauterine infections consists in preconception preparation, treatment of STDs before pregnancy, exclusion of contact between a pregnant woman and infectious patients, and correction of a pregnancy management program for women at risk. Women who have not previously had rubella and have not received rubella vaccinations should be vaccinated no later than 3 months before the expected pregnancy. In some cases, intrauterine infections may be the basis for artificial termination of pregnancy.

You can share your medical history, what helped you in the treatment of intrauterine infections.

Sources

1. self-treatment. In case of pain or other exacerbation of the disease, only the attending physician should prescribe diagnostic tests. For diagnosis and proper treatment, you should contact your doctor.

   Intrauterine infection of the fetus: a modern view of the problem

   The progressive increase in the number of cases of intrauterine infection of the fetus is one of the most urgent problems of modern obstetrics and perinatology. This is facilitated by the polyetiology of this pathology, the lack of a clear relationship between the severity of the clinical manifestations of infection in the mother and the degree of fetal damage, the multifactorial effect of the infectious agent on the fetus.

   Despite increased attention to the problem of intrauterine infection (IUI), many questions remain unresolved. Issues of diagnosis, treatment and prevention of IUI need further research and development. Until now, there are no clear criteria for treatment tactics, data on the effectiveness of complex therapy have not been summarized.

   Epidemiology, etiology and pathogenesis of intrauterine infection

   In the development of an infectious process in the fetus, the type of pathogen, its virulence, the ways of infection from mother to fetus, the protective reserves of the mother’s body and the ability of the fetus to immune response are important [11].

   According to modern data [10, 20], the number of cases of IUI varies widely from 6 to 70%. Recently, the structure of the infectious morbidity of pregnant women, parturient women and puerperas, as well as the fetus and newborn has changed [5, 8, 14]. It has been proven that the causative agents of IUI are more than 27 types of bacteria, many viruses, parasites, 6 types of fungi, 4 types of protozoa and rickettsia. So, according to a number of researchers [8, 14, 30], chlamydia (17-50%) and viruses (herpes simplex virus, HSV – 7-47%, cytomegalovirus, CMV – 28-9%) are considered to be the predominant pathogens of antenatal infections.1.6%, enteroviruses – 8-17%). The causative agents of intranatal infections are group B streptococcus (3-12%), staphylococci (1-9%), fungi of the genus Candida (3-7%). Associations of pathogens occupy a leading position (75-95%).

   It is known that most bacteria exist in nature in the form of specifically organized biofilms (biofilms) [2, 25, 27]. This form of existence creates a lot of advantages for bacteria. Bacteria in biofilms have an increased survival rate in the presence of aggressive substances, immune defense factors, and antibiotics [27]. In this regard, one of the main problems of practical medicine is the problem of treating diseases of microbial origin.

   In our study [15, 17], based on the results of bacteriological analysis of the species composition of the vaginal biotope, the strongest influence of Streptococcus faecalis (p=0.00171), E. coli (p=0.01424) and Staphylococcus epidermidis 901 67 (p=0.02714) for intrauterine infection of the fetus. When assessing the pathogens identified in the cervical canal of pregnant women by polymerase chain reaction (PCR) and enzyme immunoassay (ELISA), the following was established: in the group without the implementation of IUI, mycoplasma, chlamydia and ureaplasma accounted for 8%, CMV – 20%, HSV – 36%, candida – 3%, associations – 60%. When analyzing a group of newborns with the implementation of IUI, the most common pathogens were identified. Thus, mycoplasmas, chlamydia and HSV were found in 50%, CMV infection was detected in 45% of cases, ureaplasmas (20%) and candida (15%) were less common, associations were observed in 95%. The frequency of detection of pathogenic pathogens in newborns with signs of IUI was higher than in patients without infection.

   In the pathogenesis of IUI, there are “maternal”, “afterbirth”, “fetal” stages of development [23]:

   “Maternal” stage reflects the beginning of the infectious process within the lower parts of the urogenital tract.

   The “following” stage occurs with hematogenous spread of the inflammatory process, occurs with bacteremia and viremia.

   At the “fetal” stage, the infectious process spreads to the organs and tissues of the fetus. This occurs when the uteroplacental and placental-fetal antimicrobial barrier, the boundary of which is the layer of chorionic epithelium, is inconsistent.

   The main source of infection in IUI is the mother of the child, from whose body the pathogen enters the fetus (vertical transmission mechanism). In this case, infection occurs both by ascending, transplacental and transovarial routes, as well as by contact and aspiration (directly during childbirth) routes. Moreover, for antenatal infections, the hematogenous route is most typical, and for intranatal infections, the ascending route of infection [4, 10, 20, 21].

   The effect of IUI on the embryo and fetus is the effect of a complex of the following factors [22]:

   1. Pathological effect of microorganisms and their toxins (infectious disease, fetal hypoxia, fetal growth retardation).

   2. Violation of the process of implantation and placentation (low placentation, placenta previa).

   3. Decreased metabolic processes and immune defense of the fetus.

   The duration of pregnancy is of particular importance in the pathogenesis of the onset and development of IUI [13, 22]. The fetus does not react to infectious antigens until the 14th week of pregnancy, since it lacks immunocompetent cells, immunoglobulins and does not show immune reactions. With the beginning of the second trimester of pregnancy, the mechanism of action of ascending infection changes due to the merger of decidua vera and decidua capsularis into a single complex decidua parietalis. During this time, ascending infection may enter the fetus from the vagina or cervical canal. From this period of pregnancy, the internal pharynx of the cervical canal comes into contact with the water membranes of the fetus and, in the presence of infection, microorganisms penetrate into the amniotic fluid. Amniotic fluid acquires antimicrobial properties only after the 20th week of pregnancy, when, in response to the action of an infectious agent, an inflammatory proliferative reaction develops, which limits further penetration of the infection due to the appearance of lysozyme, complement, interferons, immunoglobulins [1, 22]. In the III trimester of pregnancy, the antibacterial protection of amniotic fluid increases. During this period, the role of the exudative component prevails in the inflammatory reaction of the fetal tissues, when inflammatory leukocyte reactions develop in the fetus (encephalitis, hepatitis, pneumonia, interstitial nephritis) in response to infection [22].

   Particularly dangerous in IUI in the II and III trimesters of pregnancy is damage to the fetal brain, which can lead to mental retardation, delayed psychomotor development of children [3, 7]. Intrauterine infection of the CNS structures by pathogens in the fetus is accompanied by various severe disorders in the formation of the brain (hydrocephalus, subependymal cysts, cystic degeneration of the brain substance, anomalies in the development of the cortex, microcephaly). It is also possible to develop ventriculitis (deformity of the choroid plexus, heterogeneity or doubling of the reflection from the ependyma of the ventricles) [11].

   Thus, infection of the fetus in the later stages of pregnancy does not, as a rule, lead to the formation of gross malformations, but can disrupt the functional mechanisms of cell and tissue differentiation [10, 11, 13].

   Changes in the condition of the fetus and the functioning of the fetoplacental system caused by intrauterine infection of the fetus affect the composition and properties of the amniotic fluid [1, 9, 26, 30]. When an infectious agent enters the amniotic fluid, it reproduces unhindered, followed by the development of chorioamnionitis [1, 9]. The fetus is in an infected environment, which creates favorable conditions for infection of the fetus by contact, i.e. through the skin, mucous membranes, respiratory and gastrointestinal tracts.

   The syndrome of “amniotic fluid infection” develops, the mechanism of which is presented as follows [20]:

   1. Ingestion and aspiration of infected water in a newborn shows signs of intrauterine infection (pneumonia, enterocolitis, vesiculosis, omphalitis, conjunctivitis, etc.).

   2. At the same time, microorganisms, spreading through the membranes or between them, reach the basal plate of the placenta (deciduitis). Further spread of the inflammatory reaction leads to the development of chorionitis (placentitis), manifested by leukocyte infiltration of the intravillous space and endovasculitis in the chorionic plate. Vasculitis in the decidua, stem and terminal villi leads to vascular obliteration, the appearance of infarcts, calcifications, massive fibrinoid deposits, which can manifest as “premature maturation of the placenta. ”

   3. Polyhydramnios in intrauterine infection is usually secondary and is a manifestation of damage to the kidneys or urinary tract of the fetus. The reason for its development is also a change in the ratio of the processes of production and resorption of amniotic fluid by the cells of the amniotic epithelium against the background of amnionitis.

   4. In the genesis of the symptom complex of placental insufficiency in IUI, the main role belongs to vascular disorders.

   5. Typical manifestations of intrauterine infection are miscarriage and premature birth [24]. Premature development of labor activity and untimely rupture of the membranes are due to the action of bacterial phospholipases that trigger the prostaglandin cascade and the damaging effect of inflammatory toxins on the membranes.

   6. Due to the fact that phospholipases of gram-negative bacteria contribute to the destruction of surfactant in the lungs of the fetus, the newborn develops respiratory disorders.

   In modern literature [4, 9, 29] there are many works devoted to the study of the relationship between immunological parameters and the severity of the infectious-inflammatory process during pregnancy. Increasingly, in foreign and domestic literature, data appear on the relationship between bacterial invasion and cytokine synthesis by amnion, chorion, decidua, and fetal tissues [5, 29]. The multiplication of microorganisms in the amniotic fluid leads to an increase in the level of lipopolysaccharides, which activate the synthesis of cytokines by fetal trophoblast cells. It seems promising in IUI to study changes in the cytokine system, which provides the processes of intercellular cooperation, growth and differentiation of lymphoid cells, hematopoiesis, and neuroimmunoendocrine interactions. Cytokines in the pre-implantation period and during the development of pregnancy are actively produced by many maternal and embryonic cells, in particular, decidual cells of the uterus and trophoblast cells. It was found that cell cultures have different ability to synthesize cytokines under the influence of lipopolysaccharides. Thus, tumor necrosis factor (TNF) is produced by amnion cells, interleukins (IL)-6 and IL-8 are produced by amnion and chorion, and IL-1 is produced only by chorion [9, 11, 28]. According to N.V. Ordzhonikidze [14], of the many pro-inflammatory (IL-1, IL-2, IL-6, IL-8, IL-15, TNF, etc.) and anti-inflammatory (IL-4, IL-10, IL-13, transforming growth factor, etc.) cytokines, IL-1, IL-6, IL-10, TNF are considered the main markers of the inflammatory process in human tissues and organs [9, 16, 28].

   Clinical characteristics of intrauterine infection

   In the pre-implantation period, under the influence of an infectious agent, the embryo dies (alternative inflammation) or continues to develop.

   Infectious damage to the embryo at 3-12 weeks is usually associated with a viral infection that freely penetrates the chorion. The fetus does not yet have anti-infective protection systems, and during the period of organogenesis, IUI placentation leads to the formation of malformations (teratogenic) or death of the embryo (embryotoxic effect) [5, 23].

   Infectious fetopathy occurs from the 16th-27th week of gestation, when the infection in the fetus generalizes, the formation of pseudomalformations (myocardial fibroelastosis, polycystic lung disease, hydrocephalus, hydronephrosis) occurs. When infected after 28 weeks, the fetus acquires the ability to a specific local reaction to the introduction of the pathogen, as a result, IUI (encephalitis, pneumonia, hepatitis, interstitial nephritis), miscarriage, intrauterine growth retardation, and fetal death are possible [2, 3, 10].

   Currently, the following types of intrauterine lesions in IUI are distinguished [20, 21]:

   – blastopathy – with a gestation period of 0-14 days; possible death of the embryo, spontaneous miscarriage or the formation of a systemic pathology similar to genetic diseases;

   – embryopathy – with a period of 15-75 days; characteristic malformations at the organ or cellular levels (true malformations), spontaneous miscarriage;

   – early fetopathy – with a period of 76-180 days; characteristic is the development of a generalized inflammatory reaction with a predominance of alterative and exudative components and an outcome in fibrosclerotic deformities of organs (false defects), abortion;

   – late fetopathy – with a period of 181 days before delivery; it is possible to develop a manifest inflammatory reaction with damage to various organs and systems (hepatitis, encephalitis, thrombocytopenia, pneumonia).

   IUI often does not have clear clinical manifestations [4, 10, 15, 17]. Rarely, the first signs in a newborn are present immediately after birth, more often they appear during the first 3 days of life. When infected in the postnatal period, the symptoms of the infectious process are detected at a later date. Clinical manifestations of congenital bacterial or mycotic skin lesions in a newborn may have the character of vesiculo-pustulosis [4]. Conjunctivitis, rhinitis and otitis media that appeared on the 1st-3rd day of life can also be manifestations of IUI. Congenital aspiration pneumonia can also appear on the 2-3rd day of life. From the moment of birth, children have signs of respiratory failure: shortness of breath, cyanosis, often dullness of percussion sound and small bubbling moist rales. The course of intrauterine pneumonia is severe, because as a result of aspiration, large areas of the lung (lower and middle lobes) are turned off from breathing due to bronchial obstruction with infected amniotic fluid containing an admixture of meconium, fetal skin scales. Enterocolitis in newborns occurs as a result of the penetration of the pathogen along with the amniotic fluid into the gastrointestinal tract. Dyspeptic symptoms usually develop on the 2-3rd day of life. Characterized by sluggish sucking, regurgitation, bloating, hepatosplenomegaly, expansion of the venous network of the anterior abdominal wall, frequent loose stools. In the microbiological study of intestinal contents, the predominance of Klebsiella, Proteus and Pseudomonas aeruginosa. Damage to the central nervous system during IUI in newborns can be both primary (meningitis, encephalitis) and secondary, due to intoxication. With damage to the choroid plexuses of the lateral ventricles of the brain, congenital hydrocephalus develops. It is necessary to pay attention to such symptoms as lethargy, poor sucking, regurgitation, delayed recovery or secondary weight loss, delayed healing of the umbilical wound, development of omphalitis. Typical symptoms of infectious intoxication in a newborn are respiratory and tissue metabolism disorders. There is a pale cyanotic coloration of the skin with a pronounced vascular pattern. Intoxication is accompanied by a violation of the excretory function of the liver and kidneys, an increase in the spleen and peripheral lymph nodes.

   Modern methods of diagnosing intrauterine infections

   The prevalence of IUI among the causes of adverse outcomes, the high level of infection in pregnant women and puerperas necessitate the search for reliable methods for its diagnosis. The non-specificity of the clinical manifestations of IUI creates diagnostic difficulties, which dictates the need for the combined use of clinical and laboratory research methods. In the last decade, the main methods for diagnosing IUI have been bacteriological and immunological [10, 11, 21].

   There are 3 stages in the diagnosis of intrauterine infection: 1) diagnosis during pregnancy; 2) early diagnosis at the time of birth; 3) diagnosis in the development of clinical signs of infection in the early neonatal period [12].

   Of the non-invasive methods of prenatal diagnosis of IUI, the most informative are ultrasound and Doppler sonography [6, 7, 15, 26]. Direct methods of laboratory diagnostics (cordocentesis, dark-field microscopy, PCR, ELISA, culture) can detect the pathogen in biological fluids or tissue biopsies of an infected child. Indirect methods for diagnosing IUI include clinical symptoms of the mother, ultrasound, and help to make only a presumptive diagnosis of IUI [10, 17, 21]. Screening tests for IUI in newborns include studies of smears of amniotic fluid, placenta, cultures of cord blood and stomach contents of the newborn, and sometimes blood culture [6, 7, 10]. The “gold standard” for post-diagnosis of IUI is the histological examination of the placenta, umbilical cord, and fetal membranes [4, 14, 23].

   Any changes in homeostasis in the mother’s body are reflected in the cellular and chemical parameters of the amniotic fluid, which very finely characterize the course of the pathological process, and therefore the amniotic fluid can serve as an important diagnostic material [1, 6, 16]. According to I.V. Bakhareva [1], the most significant in the diagnosis of IUI is the determination of the antimicrobial activity of the amniotic fluid, based on the migration of leukocytes in it when bacteria accumulate in the amniotic membrane, exceeding 103 CFU/ml. The appearance of a large number of leukocytes in the amniotic fluid, an increase in cytosis due to epithelial cells without detecting microflora may indicate IUI.

   Currently, great importance is attached to ultrasound research methods, which can be used to determine indirect signs of fetal IUI (polyhydramnios, ventriculomegaly, microcephaly, hepatomegaly, placental thickness increase, finely dispersed suspension in amniotic fluid) and structural changes in various organs [4, 11, 18, 26].

   We have developed the necessary list of diagnostic measures for the early detection of IUI [19].

   The complex examination of pregnant women included:

   1. General clinical and biochemical blood and urine tests with the definition of standard indicators.

   2. Determination of TORCH-complex pathogens by PCR in vaginal swabs, amniotic fluid.

   3. Determination of blood antibodies to chlamydia, mycoplasmas and ureaplasmas, CMV and HSV by ELISA.

   4. Carrying out an amine test, pH-metry of vaginal contents.

   5. Bacterioscopic examination of the contents of the vagina, cervical canal and urethra.

   6. Bacteriological examination of the maternal surface of the placenta, amniotic fluid, intestinal contents.

   7. Determination of the level of pro-inflammatory (IL-1β, TNF) and anti-inflammatory (IL-10) cytokines in amniotic fluid, maternal venous blood serum and fetal cord blood.

   8. Ultrasound scanning of the fetus, amniotic fluid and placenta.

   9. Histomorphological examination of the placenta.

   Newborn examination complex included:

   1. Apgar score, measurement of body weight and length at birth, dynamics of body weight gain until discharge from the maternity hospital.